An Updated Review on the Significance of DNA and Protein Methyltransferases and De-methylases in Human Diseases: From Molecular Mechanism to Novel Therapeutic Approaches


Цитировать

Полный текст

Аннотация

Epigenetic mechanisms are crucial in regulating gene expression. These mechanisms include DNA methylation and histone modifications, like methylation, acetylation, and phosphorylation. DNA methylation is associated with gene expression suppression; however, histone methylation can stimulate or repress gene expression depending on the methylation pattern of lysine or arginine residues on histones. These modifications are key factors in mediating the environmental effect on gene expression regulation. Therefore, their aberrant activity is associated with the development of various diseases. The current study aimed to review the significance of DNA and histone methyltransferases and demethylases in developing various conditions, like cardiovascular diseases, myopathies, diabetes, obesity, osteoporosis, cancer, aging, and central nervous system conditions. A better understanding of the epigenetic roles in developing diseases can pave the way for developing novel therapeutic approaches for affected patients.

Об авторах

Mohammad Ghanbari

Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz

Email: info@benthamscience.net

Negin Khosroshahi

Department of Biology, Faculty of Basic Sciences, Azarbaijan Shahid Madani University

Email: info@benthamscience.net

Maryam Alamdar

Department of Genetics Sciences, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University

Email: info@benthamscience.net

Adel Abdi

Department of Animal Biology, Faculty of Natural Sciences,, University of Tabriz

Email: info@benthamscience.net

Aida Aghazadeh

Department of Animal Biology, Faculty of Natural Sciences,, University of Tabriz

Email: info@benthamscience.net

Mohammad Feizi

Department of Animal Biology, Faculty of Natural Sciences,, University of Tabriz

Email: info@benthamscience.net

Mehdi Haghi

Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz

Автор, ответственный за переписку.
Email: info@benthamscience.net

Список литературы

  1. Greer, E.L.; Shi, Y. Histone methylation: A dynamic mark in health, disease and inheritance. Nat. Rev. Genet., 2012, 13(5), 343-357. doi: 10.1038/nrg3173 PMID: 22473383
  2. Parkel, S.; Lopez-Atalaya, J.P.; Barco, A. Histone H3 lysine methylation in cognition and intellectual disability disorders. Learn. Mem., 2013, 20(10), 570-579. doi: 10.1101/lm.029363.112 PMID: 24045506
  3. Faundes, V.; Newman, W.G.; Bernardini, L.; Canham, N.; Clayton-Smith, J.; Dallapiccola, B.; Davies, S.J.; Demos, M.K.; Goldman, A.; Gill, H.; Horton, R.; Kerr, B.; Kumar, D.; Lehman, A.; McKee, S.; Morton, J.; Parker, M.J.; Rankin, J.; Robertson, L.; Temple, I.K.; Banka, S. Histone lysine methylases and demethylases in the landscape of human developmental disorders. Am. J. Hum. Genet., 2018, 102(1), 175-187. doi: 10.1016/j.ajhg.2017.11.013 PMID: 29276005
  4. Bannister, A.J.; Kouzarides, T. Regulation of chromatin by histone modifications. Cell Res., 2011, 21(3), 381-395. doi: 10.1038/cr.2011.22 PMID: 21321607
  5. Barski, A.; Cuddapah, S.; Cui, K.; Roh, T.Y.; Schones, D.E.; Wang, Z.; Wei, G.; Chepelev, I.; Zhao, K. High-resolution profiling of histone methylations in the human genome. Cell, 2007, 129(4), 823-837. doi: 10.1016/j.cell.2007.05.009 PMID: 17512414
  6. Zhang, J.; Jing, L.; Li, M.; He, L.; Guo, Z. Regulation of histone arginine methylation/demethylation by methylase and demethylase. Mol. Med. Rep., 2019, 19(5), 3963-3971. doi: 10.3892/mmr.2019.10111 PMID: 30942418
  7. Rao, V.K.; Pal, A.; Taneja, R. A drive in SUVs: From development to disease. Epigenetics, 2017, 12(3), 177-186. doi: 10.1080/15592294.2017.1281502 PMID: 28106510
  8. Bedford, M.T.; Richard, S. Arginine methylation. Mol. Cell, 2005, 18(3), 263-272. doi: 10.1016/j.molcel.2005.04.003 PMID: 15866169
  9. Hwang, J.W.; Cho, Y.; Bae, G.U.; Kim, S.N.; Kim, Y.K. Protein arginine methyltransferases: Promising targets for cancer therapy. Exp. Mol. Med., 2021, 53(5), 788-808. doi: 10.1038/s12276-021-00613-y PMID: 34006904
  10. Tewary, S.K.; Zheng, Y.G.; Ho, M.C. Protein arginine methyltransferases: Insights into the enzyme structure and mechanism at the atomic level. Cell. Mol. Life Sci., 2019, 76(15), 2917-2932. doi: 10.1007/s00018-019-03145-x PMID: 31123777
  11. Zurita-Lopez, C.I.; Sandberg, T.; Kelly, R.; Clarke, S.G. Human protein arginine methyltransferase 7 (PRMT7) is a type III enzyme forming ω-NG-monomethylated arginine residues. J. Biol. Chem., 2012, 287(11), 7859-7870. doi: 10.1074/jbc.M111.336271 PMID: 22241471
  12. Lee, Y.H.; Stallcup, M.R. Minireview: Protein arginine methylation of nonhistone proteins in transcriptional regulation. Mol. Endocrinol., 2009, 23(4), 425-433. doi: 10.1210/me.2008-0380 PMID: 19164444
  13. Lukinović, V.; Casanova, A.G.; Roth, G.S.; Chuffart, F.; Reynoird, N. Lysine methyltransferases signaling: Histones are just the tip of the iceberg. Curr. Protein Pept. Sci., 2020, 21(7), 655-674. doi: 10.2174/1871527319666200102101608 PMID: 31894745
  14. Morera, L.; Lübbert, M.; Jung, M. Targeting histone methyltransferases and demethylases in clinical trials for cancer therapy. Clin. Epigenetics, 2016, 8(1), 57. doi: 10.1186/s13148-016-0223-4 PMID: 27222667
  15. Shi, J.; Xu, J.; Chen, Y.E.; Li, J.S.; Cui, Y.; Shen, L.; Li, J.J.; Li, W. The concurrence of DNA methylation and demethylation is associated with transcription regulation. Nat. Commun., 2021, 12(1), 5285. doi: 10.1038/s41467-021-25521-7 PMID: 34489442
  16. Bergmann, O.; Bhardwaj, R.D.; Bernard, S.; Zdunek, S.; Barnabé-Heider, F.; Walsh, S.; Zupicich, J.; Alkass, K.; Buchholz, B.A.; Druid, H.; Jovinge, S.; Frisén, J. Evidence for cardiomyocyte renewal in humans. Science, 2009, 324(5923), 98-102. doi: 10.1126/science.1164680 PMID: 19342590
  17. Ai, S.; Yu, X.; Li, Y.; Peng, Y.; Li, C.; Yue, Y.; Tao, G.; Li, C.; Pu, W.T.; He, A. Divergent requirements for EZH1 in heart development versus regeneration. Circ. Res., 2017, 121(2), 106-112. doi: 10.1161/CIRCRESAHA.117.311212 PMID: 28512107
  18. Cao, R.; Wang, L.; Wang, H.; Xia, L.; Erdjument-Bromage, H.; Tempst, P.; Jones, R.S.; Zhang, Y. Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science, 2002, 298(5595), 1039-1043. doi: 10.1126/science.1076997 PMID: 12351676
  19. Yang, J.; Kaur, K.; Edwards, J.G.; Eisenberg, C.A.; Eisenberg, L.M. Inhibition of histone methyltransferase, histone deacetylase, and β-catenin synergistically enhance the cardiac potential of bone marrow cells. Stem Cells Int., 2017, 2017, 3464953.
  20. Warren, J.S.; Tracy, C.M.; Miller, M.R.; Makaju, A.; Szulik, M.W.; Oka, S.; Yuzyuk, T.N.; Cox, J.E.; Kumar, A.; Lozier, B.K.; Wang, L.; Llana, J.G.; Sabry, A.D.; Cawley, K.M.; Barton, D.W.; Han, Y.H.; Boudina, S.; Fiehn, O.; Tucker, H.O.; Zaitsev, A.V.; Franklin, S. Histone methyltransferase Smyd1 regulates mitochondrial energetics in the heart. Proc. Natl. Acad. Sci. , 2018, 115(33), E7871-E7880. doi: 10.1073/pnas.1800680115 PMID: 30061404
  21. Ono, T.; Kamimura, N.; Matsuhashi, T.; Nagai, T.; Nishiyama, T.; Endo, J.; Hishiki, T.; Nakanishi, T.; Shimizu, N.; Tanaka, H.; Ohta, S.; Suematsu, M.; Ieda, M.; Sano, M.; Fukuda, K.; Kaneda, R. The histone 3 lysine 9 methyltransferase inhibitor chaetocin improves prognosis in a rat model of high salt diet-induced heart failure. Sci. Rep., 2017, 7(1), 39752. doi: 10.1038/srep39752 PMID: 28051130
  22. Steffensen, T.S.; Spicer, D.E. Congenital coronary artery anomalies for the pathologist. Fetal Pediatr. Pathol., 2014, 33(5-6), 268-288. doi: 10.3109/15513815.2014.966182 PMID: 25329249
  23. Yi, X.; Jiang, X.; Li, X.; Jiang, D.S. Histone lysine methylation and congenital heart disease: From bench to bedside. Int. J. Mol. Med., 2017, 40(4), 953-964. doi: 10.3892/ijmm.2017.3115 PMID: 28902362
  24. Schwenty-Lara, J.; Nürnberger, A.; Borchers, A. Loss of function of Kmt2d, a gene mutated in Kabuki syndrome, affects heart development in Xenopus laevis. Dev. Dyn., 2019, 248(6), 465-476. doi: 10.1002/dvdy.39 PMID: 30980591
  25. Chen, L.; Fulcoli, F.G.; Ferrentino, R.; Martucciello, S.; Illingworth, E.A.; Baldini, A. Transcriptional control in cardiac progenitors: Tbx1 interacts with the BAF chromatin remodeling complex and regulates Wnt5a. PLoS Genet., 2012, 8(3), e1002571. doi: 10.1371/journal.pgen.1002571 PMID: 22438823
  26. Caprio, C.; Baldini, A. p53 suppression partially rescues the mutant phenotype in mouse models of DiGeorge syndrome. Proc. Natl. Acad. Sci. , 2014, 111(37), 13385-13390. doi: 10.1073/pnas.1401923111 PMID: 25197075
  27. Park, S.H.; Lee, J.E.; Sohn, Y.B.; Ko, J.M. First identified Korean family with Sotos syndrome caused by a novel intragenic mutation in NSD1. Ann. Clin. Lab. Sci., 2014, 44(2), 228-231. PMID: 24795065
  28. Nicholson, T.B.; Singh, A.K.; Su, H.; Hevi, S.; Wang, J.; Bajko, J.; Li, M.; Valdez, R.; Goetschkes, M.; Capodieci, P.; Loureiro, J.; Cheng, X.; Li, E.; Kinzel, B.; Labow, M.; Chen, T. A hypomorphic lsd1 allele results in heart development defects in mice. PLoS One, 2013, 8(4), e60913. doi: 10.1371/journal.pone.0060913 PMID: 23637775
  29. Mokou, M.; Klein, J.; Makridakis, M.; Bitsika, V.; Bascands, J.L.; Saulnier-Blache, J.S.; Mullen, W.; Sacherer, M.; Zoidakis, J.; Pieske, B.; Mischak, H.; Roubelakis, M.G.; Schanstra, J.P.; Vlahou, A. Proteomics based identification of KDM5 histone demethylases associated with cardiovascular disease. EBioMedicine, 2019, 41, 91-104. doi: 10.1016/j.ebiom.2019.02.040 PMID: 30826357
  30. de Vries, M.R.; Quax, P.H.A. Plaque angiogenesis and its relation to inflammation and atherosclerotic plaque destabilization. Curr. Opin. Lipidol., 2016, 27(5), 499-506. doi: 10.1097/MOL.0000000000000339 PMID: 27472406
  31. Zhang, Q.J.; Tran, T.A.T.; Wang, M.; Ranek, M.J.; Kokkonen-Simon, K.M.; Gao, J.; Luo, X.; Tan, W.; Kyrychenko, V.; Liao, L.; Xu, J.; Hill, J.A.; Olson, E.N.; Kass, D.A.; Martinez, E.D.; Liu, Z.P. Histone lysine dimethyl-demethylase KDM3A controls pathological cardiac hypertrophy and fibrosis. Nat. Commun., 2018, 9(1), 5230. doi: 10.1038/s41467-018-07173-2 PMID: 30531796
  32. Xu, J.; Wang, J.; Long, F.; Zhong, W.; Su, H.; Su, Z.; Liu, X. Inhibition of the cardiac fibroblast-enriched histone methyltransferase Dot1L prevents cardiac fibrosis and cardiac dysfunction. Cell Biosci., 2022, 12(1), 134. doi: 10.1186/s13578-022-00877-5 PMID: 35986422
  33. Li, F.; Li, L.; Zhang, J.; Yang, X.; Liu, Y. Histone methyltransferase DOT1L mediates the TGF-β1/Smad3 signaling pathway through epigenetic modification of SYK in myocardial infarction. Hum. Cell, 2022, 35(1), 98-110. doi: 10.1007/s13577-021-00625-w PMID: 34635982
  34. Murata, K.; Lu, W.; Hashimoto, M.; Ono, N.; Muratani, M.; Nishikata, K.; Kim, J.D.; Ebihara, S.; Ishida, J.; Fukamizu, A. PRMT1 deficiency in mouse juvenile heart induces dilated cardiomyopathy and reveals cryptic alternative splicing products. iScience, 2018, 8, 200-213. doi: 10.1016/j.isci.2018.09.023 PMID: 30321814
  35. Pyun, J.H.; Kim, H.J.; Jeong, M.H.; Ahn, B.Y.; Vuong, T.A.; Lee, D.I.; Choi, S.; Koo, S.H.; Cho, H.; Kang, J.S. Cardiac specific PRMT1 ablation causes heart failure through CaMKII dysregulation. Nat. Commun., 2018, 9(1), 5107. doi: 10.1038/s41467-018-07606-y PMID: 30504773
  36. Cai, S.; Liu, R.; Wang, P.; Li, J.; Xie, T.; Wang, M.; Cao, Y.; Li, Z.; Liu, P. PRMT5 prevents cardiomyocyte hypertrophy via symmetric dimethylating HoxA9 and repressing HoxA9 expression. Front. Pharmacol., 2020, 11, 600627. doi: 10.3389/fphar.2020.600627 PMID: 33424610
  37. Talens, R.P.; Jukema, J.W.; Trompet, S.; Kremer, D.; Westendorp, R.G.J.; Lumey, L.H.; Sattar, N.; Putter, H.; Slagboom, P.E.; Heijmans, B.T. Hypermethylation at loci sensitive to the prenatal environment is associated with increased incidence of myocardial infarction. Int. J. Epidemiol., 2012, 41(1), 106-115. doi: 10.1093/ije/dyr153 PMID: 22101166
  38. Zhu, H.; Wang, X.; Meng, X.; Kong, Y.; Li, Y.; Yang, C.; Guo, Y.; Wang, X.; Yang, H.; Liu, Z. Selenium supplementation improved cardiac functions by suppressing DNMT2-Mediated GPX1 promoter DNA methylation in AGE-induced heart failure. Oxid. Med. Cell. Longev., 2022, 2022, 5402997. doi: 10.1155/2022/5402997
  39. Judson, R.N.; Quarta, M.; Oudhoff, M.J.; Soliman, H.; Yi, L.; Chang, C.K.; Loi, G.; Vander Werff, R.; Cait, A.; Hamer, M. Inhibition of methyltransferase setd7 allows the in vitro expansion of myogenic stem cells with improved therapeutic potential. Cell Stem Cell, 2018, 22(2), 177-190. doi: 10.1016/j.stem.2017.12.010
  40. Zhao, M.J.; Xie, J.; Shu, W.J.; Wang, H.Y.; Bi, J.; Jiang, W.; Du, H.N. MiR-15b and miR-322 inhibit SETD3 expression to repress muscle cell differentiation. Cell Death Dis., 2019, 10(3), 183. doi: 10.1038/s41419-019-1432-5 PMID: 30796205
  41. Zhong, X.; Wang, Q.Q.; Li, J.W.; Zhang, Y.M.; An, X.R.; Hou, J. Ten-eleven translocation-2 (Tet2) is involved in myogenic differentiation of skeletal myoblast cells in vitro. Sci. Rep., 2017, 7(1), 43539. doi: 10.1038/srep43539 PMID: 28272491
  42. Hon, G.C.; Song, C.X.; Du, T.; Jin, F.; Selvaraj, S.; Lee, A.Y.; Yen, C.; Ye, Z.; Mao, S.Q.; Wang, B.A.; Kuan, S.; Edsall, L.E.; Zhao, B.S.; Xu, G.L.; He, C.; Ren, B. 5mC oxidation by Tet2 modulates enhancer activity and timing of transcriptome reprogramming during differentiation. Mol. Cell, 2014, 56(2), 286-297. doi: 10.1016/j.molcel.2014.08.026 PMID: 25263596
  43. Zhang, H.; Wang, S.; Zhou, Q.; Liao, Y.; Luo, W.; Peng, Z.; Ren, R.; Wang, H. Disturbance of calcium homeostasis and myogenesis caused by TET2 deletion in muscle stem cells. Cell Death Discov., 2022, 8(1), 236. doi: 10.1038/s41420-022-01041-1 PMID: 35490157
  44. Shi, K.; Lu, Y.; Chen, X.; Li, D.; Du, W.; Yu, M. Effects of Ten-Eleven Translocation-2 (Tet2) on myogenic differentiation of chicken myoblasts. Comp. Biochem. Physiol. B Biochem. Mol. Biol., 2021, 252, 110540. doi: 10.1016/j.cbpb.2020.110540 PMID: 33242661
  45. Tracy, C.M.; Warren, J.S.; Szulik, M.; Wang, L.; Garcia, J.; Makaju, A.; Russell, K.; Miller, M.; Franklin, S. The Smyd family of methyltransferases: Role in cardiac and skeletal muscle physiology and pathology. Curr. Opin. Physiol., 2018, 1, 140-152. doi: 10.1016/j.cophys.2017.10.001 PMID: 29435515
  46. Stewart, M.D.; Lopez, S.; Nagandla, H.; Soibam, B.; Benham, A.; Nguyen, J.; Valenzuela, N.; Wu, H.J.; Burns, A.R.; Rasmussen, T.L.; Tucker, H.O.; Schwartz, R.J. Mouse myofibers lacking the SMYD1 methyltransferase are susceptible to atrophy, internalization of nuclei and myofibrillar disarray. Dis. Model. Mech., 2016, 9(3), 347-359. doi: 10.1242/dmm.022491 PMID: 26935107
  47. Fujii, T.; Tsunesumi, S.; Yamaguchi, K.; Watanabe, S.; Furukawa, Y. Smyd3 is required for the development of cardiac and skeletal muscle in zebrafish. PLoS One, 2011, 6(8), e23491. doi: 10.1371/journal.pone.0023491 PMID: 21887258
  48. Proserpio, V.; Fittipaldi, R.; Ryall, J.G.; Sartorelli, V.; Caretti, G. The methyltransferase SMYD3 mediates the recruitment of transcriptional cofactors at the myostatin and c-Met genes and regulates skeletal muscle atrophy. Genes Dev., 2013, 27(11), 1299-1312. doi: 10.1101/gad.217240.113 PMID: 23752591
  49. Caretti, G.; Di Padova, M.; Micales, B.; Lyons, G.E.; Sartorelli, V. The Polycomb Ezh2 methyltransferase regulates muscle gene expression and skeletal muscle differentiation. Genes Dev., 2004, 18(21), 2627-2638. doi: 10.1101/gad.1241904 PMID: 15520282
  50. Bordoni, V.; Bagella, L. Long noncoding RNA SYISL: The crucial interaction with EZH2 in skeletal muscle differentiation and disorders. Non-coding RNA Investig., 2019, 3, 7. doi: 10.21037/ncri.2019.01.05
  51. Marchesi, I.; Fiorentino, F.P.; Rizzolio, F.; Giordano, A.; Bagella, L. The ablation of EZH2 uncovers its crucial role in rhabdomyosarcoma formation. Cell Cycle, 2012, 11(20), 3828-3836. doi: 10.4161/cc.22025 PMID: 22983009
  52. Lanzuolo, C. Epigenetic alterations in muscular disorders. Comp. Funct. Genomics, 2012, 2012, 256892. doi: 10.1155/2012/256892
  53. Bhagwat, A.S.; Vakoc, C.R. A new bump in the epigenetic landscape. Mol. Cell, 2014, 53(6), 857-858. doi: 10.1016/j.molcel.2014.03.001 PMID: 24656126
  54. Cheng, J.; Blum, R.; Bowman, C.; Hu, D.; Shilatifard, A.; Shen, S.; Dynlacht, B.D. A role for H3K4 monomethylation in gene repression and partitioning of chromatin readers. Mol. Cell, 2014, 53(6), 979-992. doi: 10.1016/j.molcel.2014.02.032 PMID: 24656132
  55. Villivalam, S.D.; You, D.; Ebert, S.M.; Kim, J.; Xiao, H.; Palacios, H.H.; Adams, C.M.; Kang, S. Skeletal muscle DNMT3A plays a necessary role in endurance exercise by regulating oxidative capacity of red muscles. bioRxiv, 2020. doi: 10.1101/2020.05.18.102400
  56. Vanlieshout, T.L.; Stouth, D.W.; Tajik, T.; Ljubicic, V. Exercise-induced protein arginine methyltransferase expression in skeletal muscle. Med. Sci. Sports Exerc., 2018, 50(3), 447-457. doi: 10.1249/MSS.0000000000001476 PMID: 29112628
  57. Advani, A.; Gilbert, R.E.; Thai, K.; Gow, R.M.; Langham, R.G.; Cox, A.J.; Connelly, K.A.; Zhang, Y.; Herzenberg, A.M.; Christensen, P.K.; Pollock, C.A.; Qi, W.; Tan, S.M.; Parving, H.H.; Kelly, D.J. Expression, localization, and function of the thioredoxin system in diabetic nephropathy. J. Am. Soc. Nephrol., 2009, 20(4), 730-741. doi: 10.1681/ASN.2008020142 PMID: 19211714
  58. Siddiqi, F.S.; Majumder, S.; Thai, K.; Abdalla, M.; Hu, P.; Advani, S.L.; White, K.E.; Bowskill, B.B.; Guarna, G.; dos Santos, C.C.; Connelly, K.A.; Advani, A. The histone methyltransferase enzyme enhancer of zeste homolog 2 protects against podocyte oxidative stress and renal injury in diabetes. J. Am. Soc. Nephrol., 2016, 27(7), 2021-2034. doi: 10.1681/ASN.2014090898 PMID: 26534922
  59. Floris, I.; Descamps, B.; Vardeu, A.; Mitić, T.; Posadino, A.M.; Shantikumar, S.; Sala-Newby, G.; Capobianco, G.; Mangialardi, G.; Howard, L.; Dessole, S.; Urrutia, R.; Pintus, G.; Emanueli, C. Gestational diabetes mellitus impairs fetal endothelial cell functions through a mechanism involving microRNA-101 and histone methyltransferase enhancer of zester homolog-2. Arterioscler. Thromb. Vasc. Biol., 2015, 35(3), 664-674. doi: 10.1161/ATVBAHA.114.304730 PMID: 25614281
  60. Zhao, Z.; Ukidve, A.; Kim, J.; Mitragotri, S. Targeting strategies for tissue-specific drug delivery. Cell, 2020, 181(1), 151-167. doi: 10.1016/j.cell.2020.02.001 PMID: 32243788
  61. Paneni, F.; Costantino, S.; Battista, R.; Castello, L.; Capretti, G.; Chiandotto, S.; Scavone, G.; Villano, A.; Pitocco, D.; Lanza, G.; Volpe, M.; Lüscher, T.F.; Cosentino, F. Adverse epigenetic signatures by histone methyltransferase Set7 contribute to vascular dysfunction in patients with type 2 diabetes mellitus. Circ. Cardiovasc. Genet., 2015, 8(1), 150-158. doi: 10.1161/CIRCGENETICS.114.000671 PMID: 25472959
  62. Kimball, A.S.; Joshi, A.; Carson, W.F., IV; Boniakowski, A.E.; Schaller, M.; Allen, R.; Bermick, J.; Davis, F.M.; Henke, P.K.; Burant, C.F.; Kunkel, S.L.; Gallagher, K.A. The histone methyltransferase MLL1 directs macrophage-mediated inflammation in wound healing and is altered in a murine model of obesity and type 2 diabetes. Diabetes, 2017, 66(9), 2459-2471. doi: 10.2337/db17-0194 PMID: 28663191
  63. Lee, K-C.; Lee, J.S.; Jo, S.; Kim, D.; Han, S.Y. High glucose induces inflammatory reactions and changes in histonemodifying enzymes in rat mesangial cells. Biomed. Res. , 2018, 29(6), 1103-1109.
  64. Balaji, S.; Napolitano, T.; Silvano, S.; Friano, M.; Garrido-Utrilla, A.; Atlija, J.; Collombat, P. Epigenetic control of pancreatic regeneration in diabetes. Genes, 2018, 9(9), 448. doi: 10.3390/genes9090448 PMID: 30205460
  65. Lu, T.T-H.; Heyne, S.; Dror, E.; Casas, E.; Leonhardt, L.; Boenke, T.; Yang, C-H.; Arrigoni, L.; Dalgaard, K.; Teperino, R. The polycomb-dependent epigenome controls β cell dysfunction, dedifferentiation, and diabetes. Cell Metab., 2018, 27(6), 1294-1308. doi: 10.1016/j.cmet.2018.04.013
  66. Santalucía, T.; Moreno, H.; Palacín, M.; Yacoub, M.H.; Brand, N.J.; Zorzano, A. A novel functional co-operation between MyoD, MEF2 and TRα1 is sufficient for the induction of GLUT4 gene transcription. J. Mol. Biol., 2001, 314(2), 195-204. doi: 10.1006/jmbi.2001.5091 PMID: 11718554
  67. Yonamine, C.Y.; Alves-Wagner, A.B.; Esteves, J.V.; Okamoto, M.M.; Correa-Giannella, M.L.; Giannella-Neto, D.; Machado, U.F. Diabetes induces tri-methylation at lysine 9 of histone 3 at Slc2a4 gene in skeletal muscle: A new target to improve glycemic control. Mol. Cell. Endocrinol., 2019, 481, 26-34. doi: 10.1016/j.mce.2018.11.006 PMID: 30528377
  68. Cheng, Y.; Yuan, Q.; Vergnes, L.; Rong, X.; Youn, J.Y.; Li, J.; Yu, Y.; Liu, W.; Cai, H.; Lin, J.D.; Tontonoz, P.; Hong, C.; Reue, K.; Wang, C.Y. KDM4B protects against obesity and metabolic dysfunction. Proc. Natl. Acad. Sci. , 2018, 115(24), E5566-E5575. doi: 10.1073/pnas.1721814115 PMID: 29844188
  69. Kesharwani, D.; Kumar, A.; Rizvi, A.; Datta, M. miR-539-5p regulates Srebf1 transcription in the skeletal muscle of diabetic mice by targeting DNA methyltransferase 3b. Mol. Ther. Nucleic Acids, 2022, 29, 718-732. doi: 10.1016/j.omtn.2022.08.013 PMID: 36090753
  70. Kesharwani, D.; Kumar, A.; Poojary, M.; Scaria, V.; Datta, M. RNA sequencing reveals potential interacting networks between the altered transcriptome and ncRNome in the skeletal muscle of diabetic mice. Biosci. Rep., 2021, 41(7), BSR20210495. doi: 10.1042/BSR20210495 PMID: 34190986
  71. Eroglu, N.; Yerlikaya, F.H.; Onmaz, D.E.; Colakoglu, M.C. Role of ChREBP and SREBP-1c in gestational diabetes: Two key players in glucose and lipid metabolism. Int. J. Diabetes Dev. Ctries., 2022, 1-5. doi: 10.1007/s13410-022-01050-x
  72. Wan, D.; Liu, C.; Sun, Y.; Wang, W.; Huang, K.; Zheng, L. MacroH2A1.1 cooperates with EZH2 to promote adipogenesis by regulating Wnt signaling. J. Mol. Cell Biol., 2017, 9(4), 325-337. doi: 10.1093/jmcb/mjx027 PMID: 28992292
  73. Wu, X.; Wang, Y.; Wang, Y.; Wang, X.; Li, J.; Chang, K.; Sun, C.; Jia, Z.; Gao, S.; Wei, J.; Xu, J.; Xu, Y.; Li, Q. GSK126 alleviates the obesity phenotype by promoting the differentiation of thermogenic beige adipocytes in diet-induced obese mice. Biochem. Biophys. Res. Commun., 2018, 501(1), 9-15. doi: 10.1016/j.bbrc.2018.04.073 PMID: 29654753
  74. Yang, Q.Y.; Liang, J.F.; Rogers, C.J.; Zhao, J.X.; Zhu, M.J.; Du, M. Maternal obesity induces epigenetic modifications to facilitate Zfp423 expression and enhance adipogenic differentiation in fetal mice. Diabetes, 2013, 62(11), 3727-3735. doi: 10.2337/db13-0433 PMID: 23884886
  75. Gupta, R.K.; Arany, Z.; Seale, P.; Mepani, R.J.; Ye, L.; Conroe, H.M.; Roby, Y.A.; Kulaga, H.; Reed, R.R.; Spiegelman, B.M. Transcriptional control of preadipocyte determination by Zfp423. Nature, 2010, 464(7288), 619-623. doi: 10.1038/nature08816 PMID: 20200519
  76. Wang, L.; Xu, S.; Lee, J.E.; Baldridge, A.; Grullon, S.; Peng, W.; Ge, K. Histone H3K9 methyltransferase G9a represses PPARγ expression and adipogenesis. EMBO J., 2012, 32(1), 45-59. doi: 10.1038/emboj.2012.306 PMID: 23178591
  77. Jang, M.K.; Kim, J.H.; Jung, M.H. Histone H3K9 demethylase JMJD2B activates adipogenesis by regulating H3K9 methylation on PPARγ and C/EBPα during adipogenesis. PLoS One, 2017, 12(1), e0168185. doi: 10.1371/journal.pone.0168185 PMID: 28060835
  78. Kang, C.; Saso, K.; Ota, K.; Kawazu, M.; Ueda, T.; Okada, H. JMJD2B/KDM4B inactivation in adipose tissues accelerates obesity and systemic metabolic abnormalities. Genes Cells, 2018, 23(9), 767-777. doi: 10.1111/gtc.12627 PMID: 30073721
  79. Ghanbari, M.; Momen Maragheh, S.; Aghazadeh, A.; Mehrjuyan, S.R.; Hussen, B.M.; Abdoli Shadbad, M.; Dastmalchi, N.; Safaralizadeh, R. Interleukin-1 in obesity-related low-grade inflammation: From molecular mechanisms to therapeutic strategies. Int. Immunopharmacol., 2021, 96, 107765. doi: 10.1016/j.intimp.2021.107765 PMID: 34015596
  80. Pan, D.; Huang, L.; Zhu, L.J.; Zou, T.; Ou, J.; Zhou, W.; Wang, Y.X. Jmjd3-mediated H3K27me3 dynamics orchestrate brown fat development and regulate white fat plasticity. Dev. Cell, 2015, 35(5), 568-583. doi: 10.1016/j.devcel.2015.11.002 PMID: 26625958
  81. Zha, L.; Li, F.; Wu, R.; Artinian, L.; Rehder, V.; Yu, L.; Liang, H.; Xue, B.; Shi, H. The histone demethylase UTX promotes brown adipocyte thermogenic program via coordinated regulation of H3K27 demethylation and acetylation. J. Biol. Chem., 2015, 290(41), 25151-25163. doi: 10.1074/jbc.M115.662650 PMID: 26306033
  82. Zhuang, L.; Jang, Y.; Park, Y.K.; Lee, J.E.; Jain, S.; Froimchuk, E.; Broun, A.; Liu, C.; Gavrilova, O.; Ge, K. Depletion of Nsd2-mediated histone H3K36 methylation impairs adipose tissue development and function. Nat. Commun., 2018, 9(1), 1796. doi: 10.1038/s41467-018-04127-6 PMID: 29728617
  83. Lee, J.; Saha, P.K.; Yang, Q.H.; Lee, S.; Park, J.Y.; Suh, Y.; Lee, S.K.; Chan, L.; Roeder, R.G.; Lee, J.W. Targeted inactivation of MLL3 histone H3–Lys-4 methyltransferase activity in the mouse reveals vital roles for MLL3 in adipogenesis. Proc. Natl. Acad. Sci. , 2008, 105(49), 19229-19234. doi: 10.1073/pnas.0810100105 PMID: 19047629
  84. Kim, D.H.; Kim, J.; Kwon, J.S.; Sandhu, J.; Tontonoz, P.; Lee, S.K.; Lee, S.; Lee, J.W. Critical roles of the histone methyltransferase MLL4/KMT2D in murine hepatic steatosis directed by ABL1 and PPARγ2. Cell Rep., 2016, 17(6), 1671-1682. doi: 10.1016/j.celrep.2016.10.023 PMID: 27806304
  85. Wang, J.; Zhang, Y.; Zhuo, Q.; Tseng, Y.; Wang, J.; Ma, Y.; Zhang, J.; Liu, J. TET1 promotes fatty acid oxidation and inhibits NAFLD progression by hydroxymethylation of PPARα promoter. Nutr. Metab. , 2020, 17(1), 46. doi: 10.1186/s12986-020-00466-8 PMID: 33292305
  86. Qian, H.; Zhao, J.; Yang, X.; Wu, S.; An, Y.; Qu, Y.; Li, Z.; Ge, H.; Li, E.; Qi, W. TET1 promotes RXRα expression and adipogenesis through DNA demethylation. Biochim. Biophys. Acta Mol. Cell Biol. Lipids, 2021, 1866(6), 158919. doi: 10.1016/j.bbalip.2021.158919 PMID: 33684567
  87. Damal Villivalam, S.; You, D.; Kim, J.; Lim, H.W.; Xiao, H.; Zushin, P.J.H.; Oguri, Y.; Amin, P.; Kang, S. TET1 is a beige adipocyte-selective epigenetic suppressor of thermogenesis. Nat. Commun., 2020, 11(1), 4313. doi: 10.1038/s41467-020-18054-y PMID: 32855402
  88. D’Ippolito, G.; Schiller, P.C.; Ricordi, C.; Roos, B.A.; Howard, G.A. Age-related osteogenic potential of mesenchymal stromal stem cells from human vertebral bone marrow. J. Bone Miner. Res., 1999, 14(7), 1115-1122. doi: 10.1359/jbmr.1999.14.7.1115 PMID: 10404011
  89. Jing, H.; Liao, L.; An, Y.; Su, X.; Liu, S.; Shuai, Y.; Zhang, X.; Jin, Y. Suppression of EZH2 prevents the shift of osteoporotic MSC fate to adipocyte and enhances bone formation during osteoporosis. Mol. Ther., 2016, 24(2), 217-229. doi: 10.1038/mt.2015.152 PMID: 26307668
  90. Dudakovic, A.; Camilleri, E.T.; Xu, F.; Riester, S.M.; McGee-Lawrence, M.E.; Bradley, E.W.; Paradise, C.R.; Lewallen, E.A.; Thaler, R.; Deyle, D.R.; Larson, A.N.; Lewallen, D.G.; Dietz, A.B.; Stein, G.S.; Montecino, M.A.; Westendorf, J.J.; van Wijnen, A.J. Epigenetic control of skeletal development by the histone methyltransferase Ezh2. J. Biol. Chem., 2015, 290(46), 27604-27617. doi: 10.1074/jbc.M115.672345 PMID: 26424790
  91. Yin, B.; Yu, F.; Wang, C.; Li, B.; Liu, M.; Ye, L. Epigenetic control of mesenchymal stem cell fate decision via histone methyltransferase Ash1l. Stem Cells, 2019, 37(1), 115-127. doi: 10.1002/stem.2918 PMID: 30270478
  92. Sun, J.; Li, J.; Li, C.; Yu, Y. Role of bone morphogenetic protein-2 in osteogenic differentiation of mesenchymal stem cells. Mol. Med. Rep., 2015, 12(3), 4230-4237. doi: 10.3892/mmr.2015.3954 PMID: 26096280
  93. Wang, C.; Wang, J.; Li, J.; Hu, G.; Shan, S.; Li, Q.; Zhang, X. KDM5A controls bone morphogenic protein 2-induced osteogenic differentiation of bone mesenchymal stem cells during osteoporosis. Cell Death Dis., 2016, 7(8), e2335-e2335. doi: 10.1038/cddis.2016.238 PMID: 27512956
  94. Yang, D.; Yu, B.; Sun, H.; Qiu, L. The roles of histone demethylase Jmjd3 in osteoblast differentiation and apoptosis. J. Clin. Med., 2017, 6(3), 24. doi: 10.3390/jcm6030024 PMID: 28241471
  95. Sun, J.; Ermann, J.; Niu, N.; Yan, G.; Yang, Y.; Shi, Y.; Zou, W. Histone demethylase LSD1 regulates bone mass by controlling WNT7B and BMP2 signaling in osteoblasts. Bone Res., 2018, 6(1), 14. doi: 10.1038/s41413-018-0015-x PMID: 29707403
  96. Yang, X.; Wang, G.; Wang, Y.; Zhou, J.; Yuan, H.; Li, X.; Liu, Y.; Wang, B. Histone demethylase KDM7A reciprocally regulates adipogenic and osteogenic differentiation via regulation of C/EBPα and canonical Wnt signalling. J. Cell. Mol. Med., 2019, 23(3), 2149-2162. doi: 10.1111/jcmm.14126 PMID: 30614617
  97. Bartl, R.; Bartl, C. Bone disorders: Biology, diagnosis, prevention, therapy; Springer, 2016.
  98. Takayanagi, H.; Kim, S.; Koga, T.; Nishina, H.; Isshiki, M.; Yoshida, H.; Saiura, A.; Isobe, M.; Yokochi, T.; Inoue, J.; Wagner, E.F.; Mak, T.W.; Kodama, T.; Taniguchi, T. Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts. Dev. Cell, 2002, 3(6), 889-901. doi: 10.1016/S1534-5807(02)00369-6 PMID: 12479813
  99. Soysa, N.S.; Alles, N. NF-κB functions in osteoclasts. Biochem. Biophys. Res. Commun., 2009, 378(1), 1-5. doi: 10.1016/j.bbrc.2008.10.146 PMID: 18992710
  100. Gao, Y.; Ge, W. The histone methyltransferase DOT1L inhibits osteoclastogenesis and protects against osteoporosis. Cell Death Dis., 2018, 9(2), 33. doi: 10.1038/s41419-017-0040-5 PMID: 29348610
  101. Tsuda, H.; Zhao, N.; Imai, K.; Ochiai, K.; Yang, P.; Suzuki, N. BIX01294 suppresses osteoclast differentiation on mouse macrophage-like Raw264.7 cells. Bosn. J. Basic Med. Sci., 2013, 13(4), 271-275. doi: 10.17305/bjbms.2013.2339 PMID: 24289765
  102. Lu, L.; Wang, L.; Wu, J.; Yang, M.; Chen, B.; Wang, H.; Gan, K. DNMT3a promotes osteoblast differentiation and alleviates osteoporosis via the PPARγ/SCD1/GLUT1 axis. Epigenomics, 2022, 14(12), 777-792. doi: 10.2217/epi-2021-0391 PMID: 35765985
  103. Nishikawa, K.; Iwamoto, Y.; Kobayashi, Y.; Katsuoka, F.; Kawaguchi, S.; Tsujita, T.; Nakamura, T.; Kato, S.; Yamamoto, M.; Takayanagi, H.; Ishii, M. DNA methyltransferase 3a regulates osteoclast differentiation by coupling to an S-adenosylmethionine–producing metabolic pathway. Nat. Med., 2015, 21(3), 281-287. doi: 10.1038/nm.3774 PMID: 25706873
  104. Zhang, M.; Gao, Y.; Li, Q.; Cao, H.; Yang, J.; Cai, X.; Xiao, J. Downregulation of DNA methyltransferase-3a ameliorates the osteogenic differentiation ability of adipose-derived stem cells in diabetic osteoporosis; Preprint, 2022. doi: 10.21203/rs.3.rs-1431482/v1
  105. Wahl, H.W.; Iwarsson, S.; Oswald, F. Aging well and the environment: Toward an integrative model and research agenda for the future. Gerontologist, 2012, 52(3), 306-316. doi: 10.1093/geront/gnr154 PMID: 22419248
  106. Su, L.; Li, H.; Huang, C.; Zhao, T.; Zhang, Y.; Ba, X.; Li, Z.; Zhang, Y.; Huang, B.; Lu, J.; Zhao, Y.; Li, X. Muscle-specific histone H3K36 dimethyltransferase SET-18 shortens lifespan of Caenorhabditis elegans by repressing daf-16a expression. Cell Rep., 2018, 22(10), 2716-2729. doi: 10.1016/j.celrep.2018.02.029 PMID: 29514099
  107. Bartke, A. Insulin and aging. Cell Cycle, 2008, 7(21), 3338-3343. doi: 10.4161/cc.7.21.7012 PMID: 18948730
  108. Sen, P.; Dang, W.; Donahue, G.; Dai, J.; Dorsey, J.; Cao, X.; Liu, W.; Cao, K.; Perry, R.; Lee, J.Y.; Wasko, B.M.; Carr, D.T.; He, C.; Robison, B.; Wagner, J.; Gregory, B.D.; Kaeberlein, M.; Kennedy, B.K.; Boeke, J.D.; Berger, S.L. H3K36 methylation promotes longevity by enhancing transcriptional fidelity. Genes Dev., 2015, 29(13), 1362-1376. doi: 10.1101/gad.263707.115 PMID: 26159996
  109. Pu, M.; Ni, Z.; Wang, M.; Wang, X.; Wood, J.G.; Helfand, S.L.; Yu, H.; Lee, S.S. Trimethylation of Lys36 on H3 restricts gene expression change during aging and impacts life span. Genes Dev., 2015, 29(7), 718-731. doi: 10.1101/gad.254144.114 PMID: 25838541
  110. Choufani, S.; Cytrynbaum, C.; Chung, B.H.Y.; Turinsky, A.L.; Grafodatskaya, D.; Chen, Y.A.; Cohen, A.S.A.; Dupuis, L.; Butcher, D.T.; Siu, M.T.; Luk, H.M.; Lo, I.F.M.; Lam, S.T.S.; Caluseriu, O.; Stavropoulos, D.J.; Reardon, W.; Mendoza-Londono, R.; Brudno, M.; Gibson, W.T.; Chitayat, D.; Weksberg, R. NSD1 mutations generate a genome-wide DNA methylation signature. Nat. Commun., 2015, 6(1), 10207. doi: 10.1038/ncomms10207 PMID: 26690673
  111. Martin-Herranz, D.E.; Aref-Eshghi, E.; Bonder, M.J.; Stubbs, T.M.; Choufani, S.; Weksberg, R.; Stegle, O.; Sadikovic, B.; Reik, W.; Thornton, J.M. Screening for genes that accelerate the epigenetic aging clock in humans reveals a role for the H3K36 methyltransferase NSD1. Genome Biol., 2019, 20(1), 146. doi: 10.1186/s13059-019-1753-9 PMID: 31409373
  112. Rondelet, G.; Dal Maso, T.; Willems, L.; Wouters, J. Structural basis for recognition of histone H3K36me3 nucleosome by human de novo DNA methyltransferases 3A and 3B. J. Struct. Biol., 2016, 194(3), 357-367. doi: 10.1016/j.jsb.2016.03.013 PMID: 26993463
  113. Rinaldi, L.; Datta, D.; Serrat, J.; Morey, L.; Solanas, G.; Avgustinova, A.; Blanco, E.; Pons, J.I.; Matallanas, D.; Von Kriegsheim, A.; Di Croce, L.; Benitah, S.A. Dnmt3a and Dnmt3b associate with enhancers to regulate human epidermal stem cell homeostasis. Cell Stem Cell, 2016, 19(4), 491-501. doi: 10.1016/j.stem.2016.06.020 PMID: 27476967
  114. Horvath, S. DNA methylation age of human tissues and cell types. Genome Biol., 2013, 14(10), R115. doi: 10.1186/gb-2013-14-10-r115 PMID: 24138928
  115. Greer, E.L.; Maures, T.J.; Hauswirth, A.G.; Green, E.M.; Leeman, D.S.; Maro, G.S.; Han, S.; Banko, M.R.; Gozani, O.; Brunet, A. Members of the H3K4 trimethylation complex regulate lifespan in a germline-dependent manner in C. elegans. Nature, 2010, 466(7304), 383-387. doi: 10.1038/nature09195 PMID: 20555324
  116. Han, S.; Brunet, A. Histone methylation makes its mark on longevity. Trends Cell Biol., 2012, 22(1), 42-49. doi: 10.1016/j.tcb.2011.11.001 PMID: 22177962
  117. Cruz, C.; Della Rosa, M.; Krueger, C.; Gao, Q.; Horkai, D.; King, M.; Field, L.; Houseley, J. Tri-methylation of histone H3 lysine 4 facilitates gene expression in ageing cells. eLife, 2018, 7, e34081. doi: 10.7554/eLife.34081 PMID: 30274593
  118. Li, L.; Greer, C.; Eisenman, R.N.; Secombe, J. Essential functions of the histone demethylase lid. PLoS Genet., 2010, 6(11), e1001221. doi: 10.1371/journal.pgen.1001221 PMID: 21124823
  119. Mei, Q.; Xu, C.; Gogol, M.; Tang, J.; Chen, W.; Yu, X.; Workman, J.L.; Li, S. Set1-catalyzed H3K4 trimethylation antagonizes the HIR/Asf1/Rtt106 repressor complex to promote histone gene expression and chronological life span. Nucleic Acids Res., 2019, 47(7), 3434-3449. doi: 10.1093/nar/gkz101 PMID: 30759223
  120. Liu, L.; Cheung, T.H.; Charville, G.W.; Hurgo, B.M.C.; Leavitt, T.; Shih, J.; Brunet, A.; Rando, T.A. Chromatin modifications as determinants of muscle stem cell quiescence and chronological aging. Cell Rep., 2013, 4(1), 189-204. doi: 10.1016/j.celrep.2013.05.043 PMID: 23810552
  121. Maures, T.J.; Greer, E.L.; Hauswirth, A.G.; Brunet, A. The H3K27 demethylase UTX-1 regulates C. elegans lifespan in a germline-independent, insulin-dependent manner. Aging Cell, 2011, 10(6), 980-990. doi: 10.1111/j.1474-9726.2011.00738.x PMID: 21834846
  122. Siebold, A.P.; Banerjee, R.; Tie, F.; Kiss, D.L.; Moskowitz, J.; Harte, P.J. Polycomb repressive complex 2 and trithorax modulate Drosophila longevity and stress resistance. Proc. Natl. Acad. Sci. USA, 2010, 107(1), 169-174. doi: 10.1073/pnas.0907739107 PMID: 20018689
  123. Orioli, D.; Dellambra, E. Epigenetic regulation of skin cells in natural aging and premature aging diseases. Cells, 2018, 7(12), 268. doi: 10.3390/cells7120268 PMID: 30545089
  124. McCauley, B.S.; Dang, W. Histone methylation and aging: Lessons learned from model systems. Biochimica et Biophysica Acta (BBA),, 2014, 1839(12), 1454-1462.
  125. Wang, J.; Jia, S.T.; Jia, S. New insights into the regulation of heterochromatin. Trends Genet., 2016, 32(5), 284-294. doi: 10.1016/j.tig.2016.02.005 PMID: 27005444
  126. Shumaker, D.K.; Dechat, T.; Kohlmaier, A.; Adam, S.A.; Bozovsky, M.R.; Erdos, M.R.; Eriksson, M.; Goldman, A.E.; Khuon, S.; Collins, F.S.; Jenuwein, T.; Goldman, R.D. Mutant nuclear lamin A leads to progressive alterations of epigenetic control in premature aging. Proc. Natl. Acad. Sci. , 2006, 103(23), 8703-8708. doi: 10.1073/pnas.0602569103 PMID: 16738054
  127. Camozzi, D.; Capanni, C.; Cenni, V.; Mattioli, E.; Columbaro, M.; Squarzoni, S.; Lattanzi, G. Diverse lamin-dependent mechanisms interact to control chromatin dynamics. Nucleus, 2014, 5(5), 427-440. doi: 10.4161/nucl.36289 PMID: 25482195
  128. Lee, J.H.; Kim, E.W.; Croteau, D.L.; Bohr, V.A. Heterochromatin: An epigenetic point of view in aging. Exp. Mol. Med., 2020, 52(9), 1466-1474. doi: 10.1038/s12276-020-00497-4 PMID: 32887933
  129. Zhang, W.; Li, J.; Suzuki, K.; Qu, J.; Wang, P.; Zhou, J.; Liu, X.; Ren, R.; Xu, X.; Ocampo, A.; Yuan, T.; Yang, J.; Li, Y.; Shi, L.; Guan, D.; Pan, H.; Duan, S.; Ding, Z.; Li, M.; Yi, F.; Bai, R.; Wang, Y.; Chen, C.; Yang, F.; Li, X.; Wang, Z.; Aizawa, E.; Goebl, A.; Soligalla, R.D.; Reddy, P.; Esteban, C.R.; Tang, F.; Liu, G.H.; Belmonte, J.C.I. A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging. Science, 2015, 348(6239), 1160-1163. doi: 10.1126/science.aaa1356 PMID: 25931448
  130. Gao, Q.; Chen, F.; Zhang, L.; Wei, A.; Wang, Y.; Wu, Z.; Cao, W. Inhibition of DNA methyltransferase aberrations reinstates antioxidant aging suppressors and ameliorates renal aging. Aging Cell, 2022, 21(1), e13526. doi: 10.1111/acel.13526 PMID: 34874096
  131. Lian, W.S.; Wu, R.W.; Chen, Y.S.; Ko, J.Y.; Wang, S.Y.; Jahr, H.; Wang, F.S. MicroRNA-29a mitigates osteoblast senescence and counteracts bone loss through oxidation resistance-1 control of FoxO3 methylation. Antioxidants, 2021, 10(8), 1248. doi: 10.3390/antiox10081248 PMID: 34439496
  132. Nebbioso, A.; Tambaro, F.P.; Dell’Aversana, C.; Altucci, L. Cancer epigenetics: Moving forward. PLoS Genet., 2018, 14(6), e1007362. doi: 10.1371/journal.pgen.1007362 PMID: 29879107
  133. Yokoyama, A. Molecular mechanisms of MLL-associated leukemia. Int. J. Hematol., 2015, 101(4), 352-361. doi: 10.1007/s12185-015-1774-4 PMID: 25773519
  134. Rao, R.C.; Dou, Y. Hijacked in cancer: the KMT2 (MLL) family of methyltransferases. Nat. Rev. Cancer, 2015, 15(6), 334-346. doi: 10.1038/nrc3929 PMID: 25998713
  135. Krivtsov, A.V.; Twomey, D.; Feng, Z.; Stubbs, M.C.; Wang, Y.; Faber, J.; Levine, J.E.; Wang, J.; Hahn, W.C.; Gilliland, D.G.; Golub, T.R.; Armstrong, S.A. Transformation from committed progenitor to leukaemia stem cell initiated by MLL–AF9. Nature, 2006, 442(7104), 818-822. doi: 10.1038/nature04980 PMID: 16862118
  136. Cao, F.; Townsend, E.C.; Karatas, H.; Xu, J.; Li, L.; Lee, S.; Liu, L.; Chen, Y.; Ouillette, P.; Zhu, J.; Hess, J.L.; Atadja, P.; Lei, M.; Qin, Z.S.; Malek, S.; Wang, S.; Dou, Y. Targeting MLL1 H3K4 methyltransferase activity in mixed-lineage leukemia. Mol. Cell, 2014, 53(2), 247-261. doi: 10.1016/j.molcel.2013.12.001 PMID: 24389101
  137. Dong, Y.; Van Tine, B.A.; Oyama, T.; Wang, P.I.; Cheng, E.H.; Hsieh, J.J. Taspase1 cleaves MLL1 to activate cyclin E for HER2/neu breast tumorigenesis. Cell Res., 2014, 24(11), 1354-1366. doi: 10.1038/cr.2014.129 PMID: 25267403
  138. Ansari, K.I.; Kasiri, S.; Mandal, S.S. Histone methylase MLL1 has critical roles in tumor growth and angiogenesis and its knockdown suppresses tumor growth in vivo. Oncogene, 2013, 32(28), 3359-3370. doi: 10.1038/onc.2012.352 PMID: 22926525
  139. Ansari, K.I.; Kasiri, S.; Mishra, B.P.; Mandal, S.S. Mixed lineage leukaemia-4 regulates cell-cycle progression and cell viability and its depletion suppresses growth of xenografted tumour in vivo. Br. J. Cancer, 2012, 107(2), 315-324. doi: 10.1038/bjc.2012.263 PMID: 22713656
  140. Rabello, D.D.A.; De Moura, C.A.; De Andrade, R.V.; Motoyama, A.B.; Silva, F.P. Altered expression of MLL methyltransferase family genes in breast cancer. Int. J. Oncol., 2013, 43(2), 653-660. doi: 10.3892/ijo.2013.1981 PMID: 23754336
  141. Ghanbari, M.; Hosseinpour-Feizi, M.; Safaralizadeh, R.; Aghazadeh, A.; Montazeri, V. Study of KMT2B (MLL2) gene expression changes in patients with breast cancer. Breast Cancer Manag., 2019, 8(2), BMT24. doi: 10.2217/bmt-2018-0016
  142. Ladopoulos, V.; Hofemeister, H.; Hoogenkamp, M.; Riggs, A.D.; Stewart, A.F.; Bonifer, C. The histone methyltransferase KMT2B is required for RNA polymerase II association and protection from DNA methylation at the MagohB CpG island promoter. Mol. Cell. Biol., 2013, 33(7), 1383-1393. doi: 10.1128/MCB.01721-12 PMID: 23358417
  143. Weirich, S.; Kudithipudi, S.; Kycia, I.; Jeltsch, A. Somatic cancer mutations in the MLL3-SET domain alter the catalytic properties of the enzyme. Clin. Epigenet., 2015, 7(1), 36. doi: 10.1186/s13148-015-0075-3 PMID: 25829971
  144. Kantidakis, T.; Saponaro, M.; Mitter, R.; Horswell, S.; Kranz, A.; Boeing, S.; Aygün, O.; Kelly, G.P.; Matthews, N.; Stewart, A.; Stewart, A.F.; Svejstrup, J.Q. Mutation of cancer driver MLL2 results in transcription stress and genome instability. Genes Dev., 2016, 30(4), 408-420. doi: 10.1101/gad.275453.115 PMID: 26883360
  145. Mo, R.; Rao, S.M.; Zhu, Y.J. Identification of the MLL2 complex as a coactivator for estrogen receptor α. J. Biol. Chem., 2006, 281(23), 15714-15720. doi: 10.1074/jbc.M513245200 PMID: 16603732
  146. Wang, X.; Chen, C.W.; Armstrong, S.A. The role of DOT1L in the maintenance of leukemia gene expression. Curr. Opin. Genet. Dev., 2016, 36, 68-72. doi: 10.1016/j.gde.2016.03.015 PMID: 27151433
  147. Daigle, S.R.; Olhava, E.J.; Therkelsen, C.A.; Basavapathruni, A.; Jin, L.; Boriack-Sjodin, P.A.; Allain, C.J.; Klaus, C.R.; Raimondi, A.; Scott, M.P.; Waters, N.J.; Chesworth, R.; Moyer, M.P.; Copeland, R.A.; Richon, V.M.; Pollock, R.M. Potent inhibition of DOT1L as treatment of MLL-fusion leukemia. Blood, 2013, 122(6), 1017-1025. doi: 10.1182/blood-2013-04-497644 PMID: 23801631
  148. Rodrigues, C.; Pattabiraman, C.; Vijaykumar, A.; Arora, R.; Narayana, S.M.; Kumar, R.V.; Notani, D.; Varga-Weisz, P.; Krishna, S.A. SUV39H1-low chromatin state characterises and promotes migratory properties of cervical cancer cells. Exp. Cell Res., 2019, 378(2), 206-216. doi: 10.1016/j.yexcr.2019.02.010 PMID: 30772380
  149. Casciello, F.; Windloch, K.; Gannon, F.; Lee, J.S. Functional role of G9a histone methyltransferase in cancer. Front. Immunol., 2015, 6, 487. doi: 10.3389/fimmu.2015.00487 PMID: 26441991
  150. Zhang, J.; Wang, Y.; Shen, Y.; He, P.; Ding, J.; Chen, Y. G9a stimulates CRC growth by inducing p53 Lys373 dimethylation-dependent activation of Plk1. Theranostics, 2018, 8(10), 2884-2895. doi: 10.7150/thno.23824 PMID: 29774081
  151. Chen, R.J.; Shun, C.T.; Yen, M.L.; Chou, C.H.; Lin, M.C. Methyltransferase G9a promotes cervical cancer angiogenesis and decreases patient survival. Oncotarget, 2017, 8(37), 62081-62098. doi: 10.18632/oncotarget.19060 PMID: 28977928
  152. Nakagawa, M.; Kitabayashi, I. Oncogenic roles of enhancer of zeste homolog 1/2 in hematological malignancies. Cancer Sci., 2018, 109(8), 2342-2348. doi: 10.1111/cas.13655 PMID: 29845708
  153. Marchesi, I.; Bagella, L. Targeting enhancer of zeste homolog 2 as a promising strategy for cancer treatment. World J. Clin. Oncol., 2016, 7(2), 135-148. doi: 10.5306/wjco.v7.i2.135 PMID: 27081636
  154. Honma, D.; Kanno, O.; Watanabe, J.; Kinoshita, J.; Hirasawa, M.; Nosaka, E.; Shiroishi, M.; Takizawa, T.; Yasumatsu, I.; Horiuchi, T.; Nakao, A.; Suzuki, K.; Yamasaki, T.; Nakajima, K.; Hayakawa, M.; Yamazaki, T.; Yadav, A.S.; Adachi, N. Novel orally bioavailable EZH1/2 dual inhibitors with greater antitumor efficacy than an EZH2 selective inhibitor. Cancer Sci., 2017, 108(10), 2069-2078. doi: 10.1111/cas.13326 PMID: 28741798
  155. Yan, M.; Yang, X.; Wang, H.; Shao, Q. The critical role of histone lysine demethylase KDM2B in cancer. Am. J. Transl. Res., 2018, 10(8), 2222-2233. PMID: 30210666
  156. Wang, H.Y.; Long, Q.Y.; Tang, S.B.; Xiao, Q.; Gao, C.; Zhao, Q.Y.; Li, Q.L.; Ye, M.; Zhang, L.; Li, L.Y.; Wu, M. Histone demethylase KDM3A is required for enhancer activation of hippo target genes in colorectal cancer. Nucleic Acids Res., 2019, 47(5), 2349-2364. doi: 10.1093/nar/gky1317 PMID: 30649550
  157. Hayami, S.; Yoshimatsu, M.; Veerakumarasivam, A.; Unoki, M.; Iwai, Y.; Tsunoda, T.; Field, H.I.; Kelly, J.D.; Neal, D.E.; Yamaue, H.; Ponder, B.A.J.; Nakamura, Y.; Hamamoto, R. Overexpression of the JmjC histone demethylase KDM5B in human carcinogenesis: Involvement in the proliferation of cancer cells through the E2F/RB pathway. Mol. Cancer, 2010, 9(1), 59. doi: 10.1186/1476-4598-9-59 PMID: 20226085
  158. Yamane, K.; Tateishi, K.; Klose, R.J.; Fang, J.; Fabrizio, L.A.; Erdjument-Bromage, H.; Taylor-Papadimitriou, J.; Tempst, P.; Zhang, Y. PLU-1 is an H3K4 demethylase involved in transcriptional repression and breast cancer cell proliferation. Mol. Cell, 2007, 25(6), 801-812. doi: 10.1016/j.molcel.2007.03.001 PMID: 17363312
  159. Xiang, Y.; Zhu, Z.; Han, G.; Ye, X.; Xu, B.; Peng, Z.; Ma, Y.; Yu, Y.; Lin, H.; Chen, A.P.; Chen, C.D. JARID1B is a histone H3 lysine 4 demethylase up-regulated in prostate cancer. Proc. Natl. Acad. Sci. , 2007, 104(49), 19226-19231. doi: 10.1073/pnas.0700735104 PMID: 18048344
  160. Shigekawa, Y.; Hayami, S.; Ueno, M.; Miyamoto, A.; Suzaki, N.; Kawai, M.; Hirono, S.; Okada, K.; Hamamoto, R.; Yamaue, H. Overexpression of KDM5B/JARID1B is associated with poor prognosis in hepatocellular carcinoma. Oncotarget, 2018, 9(76), 34320-34335. doi: 10.18632/oncotarget.26144 PMID: 30344945
  161. Yang, L.; Zha, Y.; Ding, J.; Ye, B.; Liu, M.; Yan, C.; Dong, Z.; Cui, H.; Ding, H.F. Histone demethylase KDM6B has an anti-tumorigenic function in neuroblastoma by promoting differentiation. Oncogenesis, 2019, 8(1), 3. doi: 10.1038/s41389-018-0112-0 PMID: 30631055
  162. Bae, S.C.; Choi, J.K. Tumor suppressor activity of RUNX3. Oncogene, 2004, 23(24), 4336-4340. doi: 10.1038/sj.onc.1207286 PMID: 15156190
  163. Lau, Q.C.; Raja, E.; Salto-Tellez, M.; Liu, Q.; Ito, K.; Inoue, M.; Putti, T.C.; Loh, M.; Ko, T.K.; Huang, C.; Bhalla, K.N.; Zhu, T.; Ito, Y.; Sukumar, S. RUNX3 is frequently inactivated by dual mechanisms of protein mislocalization and promoter hypermethylation in breast cancer. Cancer Res., 2006, 66(13), 6512-6520. doi: 10.1158/0008-5472.CAN-06-0369 PMID: 16818622
  164. Zheng, J.; Mei, Y.; Zhai, G.; Zhao, N.; Jia, D.; Fan, Y. Downregulation of RUNX3 has a poor prognosis and promotes tumor progress in kidney cancer. Urol. Oncol., 2020, 38(9), 740.
  165. Liu, W.; Tan, S.; Bai, X.; Ma, S.; Chen, X. Long non-coding RNA LINC01215 promotes epithelial-mesenchymal transition and lymph node metastasis in epithelial ovarian cancer through RUNX3 promoter methylation. Transl. Oncol., 2021, 14(8), 101135. doi: 10.1016/j.tranon.2021.101135 PMID: 34052627
  166. Lee, S.H.; Hyeon, D.Y.; Yoon, S.H.; Jeong, J.H.; Han, S.M.; Jang, J.W.; Nguyen, M.P.; Chi, X.Z.; An, S.; Hyun, K.; Jung, H.J.; Song, J.J.; Bae, S.C.; Kim, W.H.; Hwang, D.; Lee, Y.M. RUNX3 methylation drives hypoxia-induced cell proliferation and antiapoptosis in early tumorigenesis. Cell Death Differ., 2021, 28(4), 1251-1269. doi: 10.1038/s41418-020-00647-1 PMID: 33116296
  167. Kerimoglu, C.; Agis-Balboa, R.C.; Kranz, A.; Stilling, R.; Bahari-Javan, S.; Benito-Garagorri, E.; Halder, R.; Burkhardt, S.; Stewart, A.F.; Fischer, A. Histone-methyltransferase MLL2 (KMT2B) is required for memory formation in mice. J. Neurosci., 2013, 33(8), 3452-3464. doi: 10.1523/JNEUROSCI.3356-12.2013 PMID: 23426673
  168. Lim, D.A.; Huang, Y.C.; Swigut, T.; Mirick, A.L.; Garcia-Verdugo, J.M.; Wysocka, J.; Ernst, P.; Alvarez-Buylla, A. Chromatin remodelling factor Mll1 is essential for neurogenesis from postnatal neural stem cells. Nature, 2009, 458(7237), 529-533. doi: 10.1038/nature07726 PMID: 19212323
  169. Huang, H.S.; Matevossian, A.; Whittle, C.; Kim, S.Y.; Schumacher, A.; Baker, S.P.; Akbarian, S. Prefrontal dysfunction in schizophrenia involves mixed-lineage leukemia 1-regulated histone methylation at GABAergic gene promoters. J. Neurosci., 2007, 27(42), 11254-11262. doi: 10.1523/JNEUROSCI.3272-07.2007 PMID: 17942719
  170. Tan, S.L.; Nishi, M.; Ohtsuka, T.; Matsui, T.; Takemoto, K.; Kamio-Miura, A.; Aburatani, H.; Shinkai, Y.; Kageyama, R. Essential roles of the histone methyltransferase ESET in the epigenetic control of neural progenitor cells during development. Development, 2012, 139(20), 3806-3816. doi: 10.1242/dev.082198 PMID: 22991445
  171. Stolt, C.C.; Lommes, P.; Sock, E.; Chaboissier, M.C.; Schedl, A.; Wegner, M. The Sox9 transcription factor determines glial fate choice in the developing spinal cord. Genes Dev., 2003, 17(13), 1677-1689. doi: 10.1101/gad.259003 PMID: 12842915
  172. Koemans, T.S.; Kleefstra, T.; Chubak, M.C.; Stone, M.H.; Reijnders, M.R.F.; de Munnik, S.; Willemsen, M.H.; Fenckova, M.; Stumpel, C.T.R.M.; Bok, L.A.; Sifuentes Saenz, M.; Byerly, K.A.; Baughn, L.B.; Stegmann, A.P.A.; Pfundt, R.; Zhou, H.; van Bokhoven, H.; Schenck, A.; Kramer, J.M. Functional convergence of histone methyltransferases EHMT1 and KMT2C involved in intellectual disability and autism spectrum disorder. PLoS Genet., 2017, 13(10), e1006864. doi: 10.1371/journal.pgen.1006864 PMID: 29069077
  173. Kramer, J.M.; Kochinke, K.; Oortveld, M.A.W.; Marks, H.; Kramer, D.; de Jong, E.K.; Asztalos, Z.; Westwood, J.T.; Stunnenberg, H.G.; Sokolowski, M.B.; Keleman, K.; Zhou, H.; van Bokhoven, H.; Schenck, A. Epigenetic regulation of learning and memory by Drosophila EHMT/G9a. PLoS Biol., 2011, 9(1), e1000569. doi: 10.1371/journal.pbio.1000569 PMID: 21245904
  174. Balemans, M.C.M.; Ansar, M.; Oudakker, A.R.; van Caam, A.P.M.; Bakker, B.; Vitters, E.L.; van der Kraan, P.M.; de Bruijn, D.R.H.; Janssen, S.M.; Kuipers, A.J.; Huibers, M.M.H.; Maliepaard, E.M.; Walboomers, X.F.; Benevento, M.; Nadif Kasri, N.; Kleefstra, T.; Zhou, H.; van der Zee, C.E.E.M.; van Bokhoven, H. Reduced Euchromatin histone methyltransferase 1 causes developmental delay, hypotonia, and cranial abnormalities associated with increased bone gene expression in Kleefstra syndrome mice. Dev. Biol., 2014, 386(2), 395-407. doi: 10.1016/j.ydbio.2013.12.016 PMID: 24362066
  175. Zheng, Y.; Liu, A.; Wang, Z.J.; Cao, Q.; Wang, W.; Lin, L.; Ma, K.; Zhang, F.; Wei, J.; Matas, E.; Cheng, J.; Chen, G.J.; Wang, X.; Yan, Z. Inhibition of EHMT1/2 rescues synaptic and cognitive functions for Alzheimer’s disease. Brain, 2019, 142(3), 787-807. doi: 10.1093/brain/awy354 PMID: 30668640
  176. Chang, E.H.; Savage, M.J.; Flood, D.G.; Thomas, J.M.; Levy, R.B.; Mahadomrongkul, V.; Shirao, T.; Aoki, C.; Huerta, P.T. AMPA receptor downscaling at the onset of Alzheimer’s disease pathology in double knockin mice. Proc. Natl. Acad. Sci. USA, 2006, 103(9), 3410-3415. doi: 10.1073/pnas.0507313103 PMID: 16492745
  177. Liu, J.; Chang, L.; Song, Y.; Li, H.; Wu, Y. The role of NMDA receptors in Alzheimer’s disease. Front. Neurosci., 2019, 13, 43. doi: 10.3389/fnins.2019.00043 PMID: 30800052
  178. Wang, W.; Cao, Q.; Tan, T.; Yang, F.; Williams, J.B.; Yan, Z. Epigenetic treatment of behavioral and physiological deficits in a tauopathy mouse model. Aging Cell, 2021, 20(10), e13456. doi: 10.1111/acel.13456 PMID: 34547169
  179. Li, H.; Wang, F.; Guo, X.; Jiang, Y. Decreased MEF2A expression regulated by its enhancer methylation inhibits autophagy and may play an important role in the progression of Alzheimer’s disease. Front. Neurosci., 2021, 15, 682247. doi: 10.3389/fnins.2021.682247 PMID: 34220439
  180. Chase, K.A.; Gavin, D.P.; Guidotti, A.; Sharma, R.P. Histone methylation at H3K9: Evidence for a restrictive epigenome in schizophrenia. Schizophr. Res., 2013, 149(1-3), 15-20. doi: 10.1016/j.schres.2013.06.021 PMID: 23815974
  181. Ryu, H.; Lee, J.; Hagerty, S.W.; Soh, B.Y.; McAlpin, S.E.; Cormier, K.A.; Smith, K.M.; Ferrante, R.J. ESET/SETDB1 gene expression and histone H3 (K9) trimethylation in Huntington’s disease. Proc. Natl. Acad. Sci. USA, 2006, 103(50), 19176-19181. doi: 10.1073/pnas.0606373103 PMID: 17142323
  182. Ravache, M.; Weber, C.; Mérienne, K.; Trottier, Y. Transcriptional activation of REST by Sp1 in Huntington’s disease models. PLoS One, 2010, 5(12), e14311. doi: 10.1371/journal.pone.0014311 PMID: 21179468
  183. Cameron, D.; Blake, D.J.; Bray, N.J.; Hill, M.J. Transcriptional changes following cellular knockdown of the schizophrenia risk gene SETD1A are enriched for common variant association with the disorder. Mol. Neuropsychiatry, 2019, 5(2), 109-114. PMID: 31192223
  184. Pereira, J.D.; Sansom, S.N.; Smith, J.; Dobenecker, M.W.; Tarakhovsky, A.; Livesey, F.J. Ezh2, the histone methyltransferase of PRC2, regulates the balance between self-renewal and differentiation in the cerebral cortex. Proc. Natl. Acad. Sci. USA, 2010, 107(36), 15957-15962. doi: 10.1073/pnas.1002530107 PMID: 20798045
  185. Park, D.H.; Hong, S.J.; Salinas, R.D.; Liu, S.J.; Sun, S.W.; Sgualdino, J.; Testa, G.; Matzuk, M.M.; Iwamori, N.; Lim, D.A. Activation of neuronal gene expression by the JMJD3 demethylase is required for postnatal and adult brain neurogenesis. Cell Rep., 2014, 8(5), 1290-1299. doi: 10.1016/j.celrep.2014.07.060 PMID: 25176653
  186. Zhou, Q.; Obana, E.A.; Radomski, K.L.; Sukumar, G.; Wynder, C.; Dalgard, C.L.; Doughty, M.L. Inhibition of the histone demethylase Kdm5b promotes neurogenesis and derepresses Reln (reelin) in neural stem cells from the adult subventricular zone of mice. Mol. Biol. Cell, 2016, 27(4), 627-639. doi: 10.1091/mbc.E15-07-0513 PMID: 26739753
  187. Ambrosio, S.; Majello, B. Targeting histone demethylase LSD1/KDM1a in neurodegenerative diseases. J. Exp. Neurosci., 2018, 12. doi: 10.1177/1179069518765743 PMID: 29581704
  188. Marsit, C.J. Influence of environmental exposure on human epigenetic regulation. J. Exp. Biol., 2015, 218(1), 71-79. doi: 10.1242/jeb.106971 PMID: 25568453
  189. Perera, F.; Herbstman, J. Prenatal environmental exposures, epigenetics, and disease. Reprod. Toxicol., 2011, 31(3), 363-373. doi: 10.1016/j.reprotox.2010.12.055 PMID: 21256208
  190. Dhimolea, E.; Wadia, P.R.; Murray, T.J.; Settles, M.L.; Treitman, J.D.; Sonnenschein, C.; Shioda, T.; Soto, A.M. Prenatal exposure to BPA alters the epigenome of the rat mammary gland and increases the propensity to neoplastic development. PLoS One, 2014, 9(7), e99800. doi: 10.1371/journal.pone.0099800 PMID: 24988533
  191. Bacalini, M.G.; Friso, S.; Olivieri, F.; Pirazzini, C.; Giuliani, C.; Capri, M.; Santoro, A.; Franceschi, C.; Garagnani, P. Present and future of anti-ageing epigenetic diets. Mech. Ageing Dev., 2014, 136-137, 101-115. doi: 10.1016/j.mad.2013.12.006 PMID: 24388875
  192. Rönn, T.; Volkov, P.; Davegårdh, C.; Dayeh, T.; Hall, E.; Olsson, A.H.; Nilsson, E.; Tornberg, Å.; Dekker Nitert, M.; Eriksson, K.F.; Jones, H.A.; Groop, L.; Ling, C. A six months exercise intervention influences the genome-wide DNA methylation pattern in human adipose tissue. PLoS Genet., 2013, 9(6), e1003572. doi: 10.1371/journal.pgen.1003572 PMID: 23825961
  193. Kanherkar, R.R.; Bhatia-Dey, N.; Csoka, A.B. Epigenetics across the human lifespan. Front. Cell Dev. Biol., 2014, 2, 49. doi: 10.3389/fcell.2014.00049 PMID: 25364756
  194. Dzobo, K. Epigenomics-guided drug development: recent advances in solving the cancer treatment "jigsaw puzzle". OMICS, 2019, 23(2), 70-85. doi: 10.1089/omi.2018.0206 PMID: 30767728
  195. Chen, G.; Wang, X.; Zhang, Y.; Ru, X.; Zhou, L.; Tian, Y. H3K9 histone methyltransferase G9a ameliorates dilated cardiomyopathy via the downregulation of cell adhesion molecules. Mol. Med. Rep., 2015, 11(5), 3872-3879. doi: 10.3892/mmr.2015.3218 PMID: 25607239
  196. Madsen, A.; Höppner, G.; Krause, J.; Hirt, M.N.; Laufer, S.D.; Schweizer, M.; Tan, W.L.W.; Mosqueira, D.; Anene-Nzelu, C.G.; Lim, I.; Foo, R.S.Y.; Eschenhagen, T.; Stenzig, J.; Stenzig, J. An important role for DNMT3A-mediated DNA methylation in cardiomyocyte metabolism and contractility. Circulation, 2020, 142(16), 1562-1578. doi: 10.1161/CIRCULATIONAHA.119.044444 PMID: 32885664
  197. Dai, X.; Liu, S.; Cheng, L.; Huang, T.; Guo, H.; Wang, D.; Xia, M.; Ling, W.; Xiao, Y. Epigenetic upregulation of H19 and AMPK inhibition concurrently contribute to S-adenosylhomocysteine hydrolase deficiency-promoted atherosclerotic calcification. Circ. Res., 2022, 130(10), 1565-1582. doi: 10.1161/CIRCRESAHA.121.320251 PMID: 35410483
  198. Lan, Y.; Banks, K.M.; Pan, H.; Verma, N.; Dixon, G.R.; Zhou, T.; Ding, B.; Elemento, O.; Chen, S.; Huangfu, D.; Evans, T. Stage-specific regulation of DNA methylation by TET enzymes during human cardiac differentiation. Cell Rep., 2021, 37(10), 110095. doi: 10.1016/j.celrep.2021.110095 PMID: 34879277
  199. Fuster, J.J.; MacLauchlan, S.; Zuriaga, M.A.; Polackal, M.N.; Ostriker, A.C.; Chakraborty, R.; Wu, C.L.; Sano, S.; Muralidharan, S.; Rius, C.; Vuong, J.; Jacob, S.; Muralidhar, V.; Robertson, A.A.B.; Cooper, M.A.; Andrés, V.; Hirschi, K.K.; Martin, K.A.; Walsh, K. Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice. Science, 2017, 355(6327), 842-847. doi: 10.1126/science.aag1381 PMID: 28104796
  200. Zhang, P.; Chen, X.; Zhang, Y.; Su, H.; Zhang, Y.; Zhou, X.; Sun, M.; Li, L.; Xu, Z. Tet3 enhances IL-6 expression through up-regulation of 5-hmC in IL-6 promoter in chronic hypoxia induced atherosclerosis in offspring rats. Life Sci., 2019, 232, 116601. doi: 10.1016/j.lfs.2019.116601 PMID: 31252000
  201. Blanc, R.S.; Vogel, G.; Li, X.; Yu, Z.; Li, S.; Richard, S. Arginine methylation by PRMT1 regulates muscle stem cell fate. Mol. Cell. Biol., 2017, 37(3), e00457-e16. doi: 10.1128/MCB.00457-16 PMID: 27849571
  202. Choi, S.; Jeong, H.J.; Kim, H.; Choi, D.; Cho, S.C.; Seong, J.K.; Koo, S.H.; Kang, J.S. Skeletal muscle-specific Prmt1 deletion causes muscle atrophy via deregulation of the PRMT6-FOXO3 axis. Autophagy, 2019, 15(6), 1069-1081. doi: 10.1080/15548627.2019.1569931 PMID: 30653406
  203. Zhang, T.; Günther, S.; Looso, M.; Künne, C.; Krüger, M.; Kim, J.; Zhou, Y.; Braun, T. Prmt5 is a regulator of muscle stem cell expansion in adult mice. Nat. Commun., 2015, 6(1), 7140. doi: 10.1038/ncomms8140 PMID: 26028225
  204. Martin, L.J.; Adams, D.A.; Niedzwiecki, M.V.; Wong, M. Aberrant DNA and RNA methylation occur in spinal cord and skeletal muscle of human SOD1 mouse models of ALS and in human ALS: Targeting DNA methylation is therapeutic. Cells, 2022, 11(21), 3448. doi: 10.3390/cells11213448 PMID: 36359844
  205. Choi, D.; Oh, K.J.; Han, H.S.; Yoon, Y.S.; Jung, C.Y.; Kim, S.T.; Koo, S.H. Protein arginine methyltransferase 1 regulates hepatic glucose production in a FoxO1-dependent manner. Hepatology, 2012, 56(4), 1546-1556. doi: 10.1002/hep.25809 PMID: 22532369
  206. Ma, Y.; Liu, S.; Jun, H.; Wang, J.; Fan, X.; Li, G.; Yin, L.; Rui, L.; Weinman, S.A.; Gong, J. A critical role for hepatic protein arginine methyltransferase 1 isoform 2 in glycemic control. FASEB J., 2020, 34(11), 14863. doi: 10.1096/fj.202001061R
  207. Vurusaner, B.; Thevkar-Nages, P.; Kaur, R.; Giannarelli, C.; Garabedian, M.J.; Fisher, E.A. Loss of PRMT2 in myeloid cells in normoglycemic mice phenocopies impaired regression of atherosclerosis in diabetic mice. Sci. Rep., 2022, 12(1), 12031. doi: 10.1038/s41598-022-15349-6 PMID: 35835907
  208. Li, Y.; Peng, M.; Zeng, T.; Zheng, J.; Liao, Y.; Zhang, H.; Yang, S.; Chen, L. Protein arginine methyltransferase 4 regulates adipose tissue lipolysis in type 1 diabetic mice. Diabetes Metab. Syndr. Obes., 2020, 13, 535-544. doi: 10.2147/DMSO.S235869 PMID: 32161480
  209. Chen, Y.T.; Liao, J.W.; Tsai, Y.C.; Tsai, F.J. Inhibition of DNA methyltransferase 1 increases nuclear receptor subfamily 4 group A member 1 expression and decreases blood glucose in type 2 diabetes. Oncotarget, 2016, 7(26), 39162-39170. doi: 10.18632/oncotarget.10043 PMID: 27322146
  210. Tan, Y.; Cao, H.; Li, Q.; Sun, J. The role of transcription factor Ap1 in the activation of the Nrf2/ARE pathway through TET1 in diabetic nephropathy. Cell Biol. Int., 2021, 45(8), 1654-1665. doi: 10.1002/cbin.11599 PMID: 33760331
  211. Villivalam, S.D.; Kim, J.; Kang, S. DNMT3a and TET2 in adipocyte insulin sensitivity. Oncotarget, 2018, 9(82), 35289-35290. doi: 10.18632/oncotarget.26246 PMID: 30450156
  212. Da Li,; Cao, T.; Sun, X.; Jin, S.; Di Xie; Huang, X.; Yang, X.; Carmichael, G.G.; Taylor, H.S.; Diano, S.; Huang, Y. Hepatic TET3 contributes to type-2 diabetes by inducing the HNF4α fetal isoform. Nat. Commun., 2020, 11(1), 342. doi: 10.1038/s41467-019-14185-z PMID: 31953394
  213. Jia, Z.; Yue, F.; Chen, X.; Narayanan, N.; Qiu, J.; Syed, S.A.; Imbalzano, A.N.; Deng, M.; Yu, P.; Hu, C.; Kuang, S. Protein arginine methyltransferase PRMT5 regulates fatty acid metabolism and lipid droplet biogenesis in white adipose tissues. Adv. Sci. (Weinh.), 2020, 7(23), 2002602. doi: 10.1002/advs.202002602 PMID: 33304767
  214. Zhu, Q.; Wang, D.; Liang, F.; Tong, X.; Liang, Z.; Wang, X.; Chen, Y.; Mo, D. Protein arginine methyltransferase PRMT1 promotes adipogenesis by modulating transcription factors C/EBPβ and PPARγ. J. Biol. Chem., 2022, 298(9), 102309. doi: 10.1016/j.jbc.2022.102309
  215. Zhang, Y.; Verwilligen, R.A.F.; de Boer, M.; Sijsenaar, T.J.P.; Van Eck, M.; Hoekstra, M. PRMT4 inhibitor TP-064 impacts both inflammatory and metabolic processes without changing the susceptibility for early atherosclerotic lesions in male apolipoprotein E knockout mice. Atherosclerosis, 2021, 338, 23-29. doi: 10.1016/j.atherosclerosis.2021.11.001 PMID: 34785428
  216. Kamei, Y.; Suganami, T.; Ehara, T.; Kanai, S.; Hayashi, K.; Yamamoto, Y.; Miura, S.; Ezaki, O.; Okano, M.; Ogawa, Y. Increased expression of DNA methyltransferase 3a in obese adipose tissue: studies with transgenic mice. Obesity (Silver Spring), 2010, 18(2), 314-321. doi: 10.1038/oby.2009.246 PMID: 19680236
  217. Yang, X.; Wang, X.; Liu, D.; Yu, L.; Xue, B.; Shi, H. Epigenetic regulation of macrophage polarization by DNA methyltransferase 3b. Mol. Endocrinol., 2014, 28(4), 565-574. doi: 10.1210/me.2013-1293 PMID: 24597547
  218. Wang, X.; Cao, Q.; Yu, L.; Shi, H.; Xue, B.; Shi, H. Epigenetic regulation of macrophage polarization and inflammation by DNA methylation in obesity. JCI Insight, 2016, 1(19), e87748. doi: 10.1172/jci.insight.87748 PMID: 27882346
  219. Choi, J.H.; Jang, A.R.; Kim, D.; Park, M.J.; Lim, S.K.; Kim, M.S.; Park, J.H. PRMT1 mediates RANKL-induced osteoclastogenesis and contributes to bone loss in ovariectomized mice. Exp. Mol. Med., 2018, 50(8), 1-15. doi: 10.1038/s12276-018-0134-x PMID: 30154485
  220. Min, Z.; Xiaomeng, L.; Zheng, L.; Yangge, D.; Xuejiao, L.; Longwei, L.; Xiao, Z.; Yunsong, L.; Ping, Z.; Yongsheng, Z. Asymmetrical methyltransferase PRMT3 regulates human mesenchymal stem cell osteogenesis via miR-3648. Cell Death Dis., 2019, 10(8), 581. doi: 10.1038/s41419-019-1815-7 PMID: 31378783
  221. Dong, Y.; Song, C.; Wang, Y.; Lei, Z.; Xu, F.; Guan, H.; Chen, A.; Li, F. Inhibition of PRMT5 suppresses osteoclast differentiation and partially protects against ovariectomy-induced bone loss through downregulation of CXCL10 and RSAD2. Cell. Signal., 2017, 34, 55-65. doi: 10.1016/j.cellsig.2017.03.004 PMID: 28302565
  222. Ye, L.; Fan, Z.; Yu, B.; Chang, J.; Al Hezaimi, K.; Zhou, X.; Park, N.H.; Wang, C.Y. Histone demethylases KDM4B and KDM6B promotes osteogenic differentiation of human MSCs. Cell Stem Cell, 2012, 11(1), 50-61. doi: 10.1016/j.stem.2012.04.009 PMID: 22770241
  223. Li, B.; Zhao, J.; Ma, J.; Li, G.; Zhang, Y.; Xing, G.; Liu, J.; Ma, X. Overexpression of DNMT1 leads to hypermethylation of H19 promoter and inhibition of Erk signaling pathway in disuse osteoporosis. Bone, 2018, 111, 82-91. doi: 10.1016/j.bone.2018.03.017 PMID: 29555308
  224. Yang, C.; Tao, H.; Zhang, H.; Xia, Y.; Bai, J.; Ge, G.; Li, W.; Zhang, W.; Xiao, L.; Xu, Y.; Wang, Z.; Gu, Y.; Yang, H.; Liu, Y.; Geng, D. TET2 regulates osteoclastogenesis by modulating autophagy in OVX-induced bone loss. Autophagy, 2022, 18(12), 2817-2829. doi: 10.1080/15548627.2022.2048432 PMID: 35255774
  225. Lee, S.Y.; Vuong, T.A.; So, H.K.; Kim, H.J.; Kim, Y.B.; Kang, J.S.; Kwon, I.; Cho, H. PRMT7 deficiency causes dysregulation of the HCN channels in the CA1 pyramidal cells and impairment of social behaviors. Exp. Mol. Med., 2020, 52(4), 604-614. doi: 10.1038/s12276-020-0417-x PMID: 32269286
  226. Quan, X.; Yue, W.; Luo, Y.; Cao, J.; Wang, H.; Wang, Y.; Lu, Z. The protein arginine methyltransferase PRMT5 regulates Aβ-induced toxicity in human cells and Caenorhabditis elegans models of Alzheimer’s disease. J. Neurochem., 2015, 134(5), 969-977. doi: 10.1111/jnc.13191 PMID: 26086249
  227. Hahn, A.; Pensold, D.; Bayer, C.; Tittelmeier, J.; González-Bermúdez, L.; Marx-Blümel, L.; Linde, J.; Groß, J.; Salinas-Riester, G.; Lingner, T.; von Maltzahn, J.; Spehr, M.; Pieler, T.; Urbach, A.; Zimmer-Bensch, G. DNA methyltransferase 1 (DNMT1) function is implicated in the age-related loss of cortical interneurons. Front. Cell Dev. Biol., 2020, 8, 639. doi: 10.3389/fcell.2020.00639 PMID: 32793592
  228. Dong, E.; Gavin, D.P.; Chen, Y.; Davis, J. Upregulation of TET1 and downregulation of APOBEC3A and APOBEC3C in the parietal cortex of psychotic patients. Transl. Psychiatry, 2012, 2(9), e159-e159. doi: 10.1038/tp.2012.86 PMID: 22948384
  229. Carrillo-Jimenez, A.; Deniz, Ö.; Niklison-Chirou, M.V.; Ruiz, R.; Bezerra-Salomao, K.; Stratoulias, V.; Amouroux, R.; Yip, P.K.; Vilalta, A.; Cheray, M. TET2 regulates the neuroinflammatory response in microglia. Cell Rep., 2019, 29(3), 697-713. doi: 10.1016/j.celrep.2019.09.013
  230. Sager, S.G.; Turkyilmaz, A.; Gunbey, H.P.; Karatoprak, E.Y.; Aslan, E.S.; Akın, Y. A novel de novo TET3 loss-of-function variant in a Turkish boy presenting with neurodevelopmental delay and electrical status epilepticus during slow-wave sleep. Brain Dev., 2023, 45(2), 140-145. doi: 10.1016/j.braindev.2022.09.004 PMID: 36192301

Дополнительные файлы

Доп. файлы
Действие
1. JATS XML
Скачать

© Bentham Science Publishers, 2024