International Journal of Biomedicine. 2022;12(4):506-514.
DOI: 10.21103/Article12(4)_RA2
Originally published December 5, 2022
Many recent studies have focused on the manipulation of the epigenome to understand the mechanistic programming in health and some disease phenotypes. These studies are designed to provide suitable drug targets to cure and/or prevent the outcome of a disease condition. Autoimmune diseases (ADs), including obesity and diabetes, are of major health concern nowadays and are the root cause of several diseases of the heart, lungs, and liver. There are several epigenetic mechanisms underlying the manifestation of autoimmune disorders. The recent advances in today’s sequencing technology and genome editing have uncovered the role of epigenetic modifications in ADs. In this review, we will cover the recent discoveries and their possible application in the control of ADs by improving the long-term use of such technologies. The potential drawbacks will also be discussed so that future experiments may be designed to reduce or eliminate the risk factors associated with the use of recent discoveries in the field of medicine.
1. Li C, Tobi EW, Heijmans BT, Lumey LH. The effect of the Chinese Famine on type 2 diabetes mellitus epidemics. Nat Rev Endocrinol. 2019 Jun;15(6):313-314. doi: 10.1038/s41574-019-0195-5. PMID: 30899101.
2. Lenard NR, Berthoud HR. Central and peripheral regulation of food intake and physical activity: pathways and genes. Obesity (Silver Spring). 2008 Dec;16 Suppl 3(Suppl 3):S11-22. doi: 10.1038/oby.2008.511. PMID: 19190620; PMCID: PMC2687326.
3. Stefan N, Schick F, Häring HU. Causes, Characteristics, and Consequences of Metabolically Unhealthy Normal Weight in Humans. Cell Metab. 2017 Aug 1;26(2):292-300. doi: 10.1016/j.cmet.2017.07.008. PMID: 28768170.
4. Thaiss CA, Levy M, Grosheva I, Zheng D, Soffer E, Blacher E, et al. Hyperglycemia drives intestinal barrier dysfunction and risk for enteric infection. Science. 2018 Mar 23;359(6382):1376-1383. doi: 10.1126/science.aar3318.
5. Global BMI Mortality Collaboration, Di Angelantonio E, Bhupathiraju ShN, Wormser D, Gao P, Kaptoge S, Berrington de Gonzalez A, et al. Body-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents. Lancet. 2016 Aug 20;388(10046):776-86. doi: 10.1016/S0140-6736(16)30175-1. Epub 2016 Jul 13. PMID: 27423262; PMCID: PMC4995441.
6. Wang S, Wen F, Tessneer KL, Gaffney PM. TALEN-mediated enhancer knockout influences TNFAIP3 gene expression and mimics a molecular phenotype associated with systemic lupus erythematosus. Genes Immun. 2016 Apr;17(3):165-70. doi: 10.1038/gene.2016.4.
7. NEEL JV. Diabetes mellitus: a "thrifty" genotype rendered detrimental by "progress"? Am J Hum Genet. 1962 Dec;14(4):353-62. PMID: 13937884; PMCID: PMC1932342.
8. Hales CN, Barker DJ. Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia. 1992 Jul;35(7):595-601. doi: 10.1007/BF00400248. PMID: 1644236.
9. Crossman MK, Kazdin AE, Galbraith K, Eros L, Santos LR. Evaluating the Influence of the Presence of a Dog on Bias toward Individuals with Overweight and Obesity. Anthrozoös. 2018;31(1):77-88.
10. Gurzov EN, Stanley WJ, Pappas EG, Thomas HE, Gough DJ. The JAK/STAT pathway in obesity and diabetes. FEBS J. 2016 Aug;283(16):3002-15. doi: 10.1111/febs.13709.
11. Hao J, Zhang Y, Yan X, Yan F, Sun Y, Zeng J, Waigel S, Yin Y, Fraig MM, Egilmez NK, Suttles J, Kong M, Liu S, Cleary MP, Sauter E, Li B. Circulating Adipose Fatty Acid Binding Protein Is a New Link Underlying Obesity-Associated Breast/Mammary Tumor Development. Cell Metab. 2018 Nov 6;28(5):689-705.e5. doi: 10.1016/j.cmet.2018.07.006.
12. WHO. Obesity and overweight. 9 June 2021. Available at: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
13. Cheng J, Song J, He X, Zhang M, Hu S, Zhang S, et al. Loss of Mbd2 Protects Mice Against High-Fat Diet-Induced Obesity and Insulin Resistance by Regulating the Homeostasis of Energy Storage and Expenditure. Diabetes. 2016 Nov;65(11):3384-3395. doi: 10.2337/db16-0151. Epub 2016 Aug 23. Erratum in: Diabetes. 2017 Sep;66(9):2531. PMID: 27554473.
14. Heymsfield SB, Wadden TA. Mechanisms, Pathophysiology, and Management of Obesity. N Engl J Med. 2017 Jan 19;376(3):254-266. doi: 10.1056/NEJMra1514009. PMID: 28099824.
15. Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, et al. Identification and importance of brown adipose tissue in adult humans. N Engl J Med. 2009 Apr 9;360(15):1509-17. doi: 10.1056/NEJMoa0810780.
16. Ying W, Riopel M, Bandyopadhyay G, Dong Y, Birmingham A, Seo JB, et al. Adipose Tissue Macrophage-Derived Exosomal miRNAs Can Modulate In Vivo and In Vitro Insulin Sensitivity. Cell. 2017 Oct 5;171(2):372-384.e12. doi: 10.1016/j.cell.2017.08.035.
17. Gaudet AD, Fonken LK, Gushchina LV, Aubrecht TG, Maurya SK, Periasamy M, et al. miR-155 Deletion in Female Mice Prevents Diet-Induced Obesity. Sci Rep. 2016 Mar 8;6:22862. doi: 10.1038/srep22862.
18. Jiang H, Ding X, Cao Y, Wang H, Zeng W. Dense Intra-adipose Sympathetic Arborizations Are Essential for Cold-Induced Beiging of Mouse White Adipose Tissue. Cell Metab. 2017 Oct 3;26(4):686-692.e3. doi: 10.1016/j.cmet.2017.08.016.
19. Li G, Xie C, Lu S, Nichols RG, Tian Y, Li L, et al. Intermittent Fasting Promotes White Adipose Browning and Decreases Obesity by Shaping the Gut Microbiota. Cell Metab. 2017 Oct 3;26(4):672-685.e4. doi: 10.1016/j.cmet.2017.08.019.
20. Chen Y, Ikeda K, Yoneshiro T, Scaramozza A, Tajima K, Wang Q, et al. Thermal stress induces glycolytic beige fat formation via a myogenic state. Nature. 2019 Jan;565(7738):180-185. doi: 10.1038/s41586-018-0801-z.
21. Wielosz E, Majdan M, Dryglewska M, Suszek D. Comparison of clinical and serological parameters in female and male patients with systemic sclerosis. Reumatologia. 2015;53(6):315-20. doi: 10.5114/reum.2015.57637.
22. Assassi S, Del Junco D, Sutter K, McNearney TA, Reveille JD, Karnavas A, et al. Clinical and genetic factors predictive of mortality in early systemic sclerosis. Arthritis Rheum. 2009 Oct 15;61(10):1403-11. doi: 10.1002/art.24734.
23. Varga J, Abraham D. Systemic sclerosis: a prototypic multisystem fibrotic disorder. J Clin Invest. 2007 Mar;117(3):557-67. doi: 10.1172/JCI31139.
24. Elkon R, Zlotorynski E, Zeller KI, Agami R. Major role for mRNA stability in shaping the kinetics of gene induction. BMC Genomics. 2010 Apr 21;11:259. doi: 10.1186/1471-2164-11-259.
25. Ghosh AK, Bhattacharyya S, Lafyatis R, Farina G, Yu J, Thimmapaya B, et al. p300 is elevated in systemic sclerosis and its expression is positively regulated by TGF-β: epigenetic feed-forward amplification of fibrosis. J Invest Dermatol. 2013 May;133(5):1302-10. doi: 10.1038/jid.2012.479.
26. Altorok N, Tsou PS, Coit P, Khanna D, Sawalha AH. Genome-wide DNA methylation analysis in dermal fibroblasts from patients with diffuse and limited systemic sclerosis reveals common and subset-specific DNA methylation aberrancies. Ann Rheum Dis. 2015 Aug;74(8):1612-20. doi: 10.1136/annrheumdis-2014-205303.
27. Wang YY, Wang Q, Sun XH, Liu RZ, Shu Y, Kanekura T, et al. DNA hypermethylation of the forkhead box protein 3 (FOXP3) promoter in CD4+ T cells of patients with systemic sclerosis. Br J Dermatol. 2014 Jul;171(1):39-47. doi: 10.1111/bjd.12913.
28. Romano E, Chora I, Manetti M, Mazzotta C, Rosa I, Bellando-Randone S, et al. Decreased expression of neuropilin-1 as a novel key factor contributing to peripheral microvasculopathy and defective angiogenesis in systemic sclerosis. Ann Rheum Dis. 2016 Aug;75(8):1541-9. doi: 10.1136/annrheumdis-2015-207483.
29. Henderson J, Brown M, Horsburgh S, Duffy L, Wilkinson S, Worrell J, Stratton R, O'Reilly S. Methyl cap binding protein 2: a key epigenetic protein in systemic sclerosis. Rheumatology (Oxford). 2019 Mar 1;58(3):527-535. doi: 10.1093/rheumatology/key327.
30. Miyagawa T, Asano Y, Saigusa R, Hirabayashi M, Yamashita T, Taniguchi T, et al. A potential contribution of trappin-2 to the development of vasculopathy in systemic sclerosis. J Eur Acad Dermatol Venereol. 2019 Apr;33(4):753-760. doi: 10.1111/jdv.15387.
31. Mariotti B, Servaas NH, Rossato M, Tamassia N, Cassatella MA, Cossu M, et al. The Long Non-coding RNA NRIR Drives IFN-Response in Monocytes: Implication for Systemic Sclerosis. Front Immunol. 2019 Jan 31;10:100. doi: 10.3389/fimmu.2019.00100.
32. Angiolilli C, Marut W, van der Kroef M, Chouri E, Reedquist KA, Radstake TRDJ. New insights into the genetics and epigenetics of systemic sclerosis. Nat Rev Rheumatol. 2018 Nov;14(11):657-673. doi: 10.1038/s41584-018-0099-0.
33. Lu Q, Wu A, Tesmer L, Ray D, Yousif N, Richardson B. Demethylation of CD40LG on the inactive X in T cells from women with lupus. J Immunol. 2007 Nov 1;179(9):6352-8. doi: 10.4049/jimmunol.179.9.6352.
34. Lian X, Xiao R, Hu X, Kanekura T, Jiang H, Li Y, et al. DNA demethylation of CD40l in CD4+ T cells from women with systemic sclerosis: a possible explanation for female susceptibility. Arthritis Rheum. 2012 Jul;64(7):2338-45. doi: 10.1002/art.34376.
35. Liao J, Liang G, Xie S, Zhao H, Zuo X, Li F, et al. CD40L demethylation in CD4(+) T cells from women with rheumatoid arthritis. Clin Immunol. 2012 Oct;145(1):13-8. doi: 10.1016/j.clim.2012.07.006.
36. Oelke K, Lu Q, Richardson D, Wu A, Deng C, Hanash S, Richardson B. Overexpression of CD70 and overstimulation of IgG synthesis by lupus T cells and T cells treated with DNA methylation inhibitors. Arthritis Rheum. 2004 Jun;50(6):1850-60. doi: 10.1002/art.20255.
37. Jiang H, Xiao R, Lian X, Kanekura T, Luo Y, Yin Y, Zhang G, Yang Y, Wang Y, Zhao M, Lu Q. Demethylation of TNFSF7 contributes to CD70 overexpression in CD4+ T cells from patients with systemic sclerosis. Clin Immunol. 2012 Apr;143(1):39-44. doi: 10.1016/j.clim.2012.01.005.
38. Yin H, Zhao M, Wu X, Gao F, Luo Y, Ma L, et al. Hypomethylation and overexpression of CD70 (TNFSF7) in CD4+ T cells of patients with primary Sjögren's syndrome. J Dermatol Sci. 2010 Sep;59(3):198-203. doi: 10.1016/j.jdermsci.2010.06.011.
39. Li Y, Zhao M, Hou C, Liang G, Yang L, Tan Y, et al. Abnormal DNA methylation in CD4+ T cells from people with latent autoimmune diabetes in adults. Diabetes Res Clin Pract. 2011 Nov;94(2):242-8. doi: 10.1016/j.diabres.2011.07.027.
40. Janson PC, Linton LB, Bergman EA, Marits P, Eberhardson M, Piehl F, et al. Profiling of CD4+ T cells with epigenetic immune lineage analysis. J Immunol. 2011 Jan 1;186(1):92-102. doi: 10.4049/jimmunol.1000960.
41. Graves MC, Benton M, Lea RA, Boyle M, Tajouri L, Macartney-Coxson D, et al. Methylation differences at the HLA-DRB1 locus in CD4+ T-Cells are associated with multiple sclerosis. Mult Scler. 2014 Jul;20(8):1033-41. doi: 10.1177/1352458513516529.
42. Hedrich CM, Rauen T, Apostolidis SA, Grammatikos AP, Rodriguez Rodriguez N, Ioannidis C, et al. Stat3 promotes IL-10 expression in lupus T cells through trans-activation and chromatin remodeling. Proc Natl Acad Sci U S A. 2014 Sep 16;111(37):13457-62. doi: 10.1073/pnas.1408023111.
43. Zhao M, Tang J, Gao F, Wu X, Liang Y, Yin H, Lu Q. Hypomethylation of IL10 and IL13 promoters in CD4+ T cells of patients with systemic lupus erythematosus. J Biomed Biotechnol. 2010;2010:931018. doi: 10.1155/2010/931018.
44. Absher DM, Li X, Waite LL, Gibson A, Roberts K, Edberg J, et al. Genome-wide DNA methylation analysis of systemic lupus erythematosus reveals persistent hypomethylation of interferon genes and compositional changes to CD4+ T-cell populations. PLoS Genet. 2013;9(8):e1003678. doi: 10.1371/journal.pgen.1003678.
45. Lu Q, Kaplan M, Ray D, Ray D, Zacharek S, Gutsch D, Richardson B. Demethylation of ITGAL (CD11a) regulatory sequences in systemic lupus erythematosus. Arthritis Rheum. 2002 May;46(5):1282-91. doi: 10.1002/art.10234.
46. Kaplan MJ, Lu Q, Wu A, Attwood J, Richardson B. Demethylation of promoter regulatory elements contributes to perforin overexpression in CD4+ lupus T cells. J Immunol. 2004 Mar 15;172(6):3652-61. doi: 10.4049/jimmunol.172.6.3652.
47. Altorok N, Coit P, Hughes T, Koelsch KA, Stone DU, Rasmussen A, et al. Genome-wide DNA methylation patterns in naive CD4+ T cells from patients with primary Sjögren's syndrome. Arthritis Rheumatol. 2014 Mar;66(3):731-9. doi: 10.1002/art.38264.
48. Coit P, Jeffries M, Altorok N, Dozmorov MG, Koelsch KA, Wren JD, et al. Genome-wide DNA methylation study suggests epigenetic accessibility and transcriptional poising of interferon-regulated genes in naïve CD4+ T cells from lupus patients. J Autoimmun. 2013 Jun;43:78-84. doi: 10.1016/j.jaut.2013.04.003.
49. Garaud S, Le Dantec C, Jousse-Joulin S, Hanrotel-Saliou C, Saraux A, Mageed RA, et al. IL-6 modulates CD5 expression in B cells from patients with lupus by regulating DNA methylation. J Immunol. 2009 May 1;182(9):5623-32. doi: 10.4049/jimmunol.0802412.
50. Fali T, Le Dantec C, Thabet Y, Jousse S, Hanrotel C, Youinou P, et al. DNA methylation modulates HRES1/p28 expression in B cells from patients with Lupus. Autoimmunity. 2014 Jun;47(4):265-71. doi: 10.3109/08916934.2013.826207.
51. Nile CJ, Read RC, Akil M, Duff GW, Wilson AG. Methylation status of a single CpG site in the IL6 promoter is related to IL6 messenger RNA levels and rheumatoid arthritis. Arthritis Rheum. 2008 Sep;58(9):2686-93. doi: 10.1002/art.23758.
52. Allanore Y, Borderie D, Meune C, Lemaréchal H, Weber S, Ekindjian OG, Kahan A. Increased plasma soluble CD40 ligand concentrations in systemic sclerosis and association with pulmonary arterial hypertension and digital ulcers. Ann Rheum Dis. 2005 Mar;64(3):481-3. doi: 10.1136/ard.2003.020040.
53. Kumagai C, Kalman B, Middleton FA, Vyshkina T, Massa PT. Increased promoter methylation of the immune regulatory gene SHP-1 in leukocytes of multiple sclerosis subjects. J Neuroimmunol. 2012 May 15;246(1-2):51-7. doi: 10.1016/j.jneuroim.2012.03.003.
54. Rakyan VK, Beyan H, Down TA, Hawa MI, Maslau S, Aden D, et al. Identification of type 1 diabetes-associated DNA methylation variable positions that precede disease diagnosis. PLoS Genet. 2011 Sep;7(9):e1002300. doi: 10.1371/journal.pgen.1002300.
55. Wang Y, Fan PS, Kahaleh B. Association between enhanced type I collagen expression and epigenetic repression of the FLI1 gene in scleroderma fibroblasts. Arthritis Rheum. 2006 Jul;54(7):2271-9. doi: 10.1002/art.21948.
56. Dees C, Schlottmann I, Funke R, Distler A, Palumbo-Zerr K, Zerr P, et al. The Wnt antagonists DKK1 and SFRP1 are downregulated by promoter hypermethylation in systemic sclerosis. Ann Rheum Dis. 2014 Jun;73(6):1232-9. doi: 10.1136/annrheumdis-2012-203194.
57. Trenkmann M, Brock M, Gay RE, Kolling C, Speich R, Michel BA, Gay S, Huber LC. Expression and function of EZH2 in synovial fibroblasts: epigenetic repression of the Wnt inhibitor SFRP1 in rheumatoid arthritis. Ann Rheum Dis. 2011 Aug;70(8):1482-8. doi: 10.1136/ard.2010.143040.
58. Miao CG, Yang YY, He X, Huang C, Huang Y, Qin D, Du CL, Li J. MicroRNA-152 modulates the canonical Wnt pathway activation by targeting DNA methyltransferase 1 in arthritic rat model. Biochimie. 2014 Nov;106:149-56. doi: 10.1016/j.biochi.2014.08.016.
59. Takami N, Osawa K, Miura Y, Komai K, Taniguchi M, Shiraishi M, et al. Hypermethylated promoter region of DR3, the death receptor 3 gene, in rheumatoid arthritis synovial cells. Arthritis Rheum. 2006 Mar;54(3):779-87. doi: 10.1002/art.21637.
60. Mastronardi FG, Noor A, Wood DD, Paton T, Moscarello MA. Peptidyl argininedeiminase 2 CpG island in multiple sclerosis white matter is hypomethylated. J Neurosci Res. 2007 Jul;85(9):2006-16. doi: 10.1002/jnr.21329.
61. González S, Aguilera S, Alliende C, Urzúa U, Quest AF, Herrera L, et al. Alterations in type I hemidesmosome components suggestive of epigenetic control in the salivary glands of patients with Sjögren's syndrome. Arthritis Rheum. 2011 Apr;63(4):1106-15. doi: 10.1002/art.30212.
62. Hu N, Qiu X, Luo Y, Yuan J, Li Y, Lei W, et al. Abnormal histone modification patterns in lupus CD4+ T cells. J Rheumatol. 2008 May;35(5):804-10.
63. Zhou Y, Qiu X, Luo Y, Yuan J, Li Y, Zhong Q, Zhao M, Lu Q. Histone modifications and methyl-CpG-binding domain protein levels at the TNFSF7 (CD70) promoter in SLE CD4+ T cells. Lupus. 2011 Nov;20(13):1365-71. doi: 10.1177/0961203311413412.
64. Miao F, Smith DD, Zhang L, Min A, Feng W, Natarajan R. Lymphocytes from patients with type 1 diabetes display a distinct profile of chromatin histone H3 lysine 9 dimethylation: an epigenetic study in diabetes. Diabetes. 2008 Dec;57(12):3189-98. doi: 10.2337/db08-0645.
65. Miao F, Chen Z, Zhang L, Liu Z, Wu X, Yuan YC, Natarajan R. Profiles of epigenetic histone post-translational modifications at type 1 diabetes susceptible genes. J Biol Chem. 2012 May 11;287(20):16335-45. doi: 10.1074/jbc.M111.330373.
66. Zhang Z, Song L, Maurer K, Petri MA, Sullivan KE. Global H4 acetylation analysis by ChIP-chip in systemic lupus erythematosus monocytes. Genes Immun. 2010 Mar;11(2):124-33. doi: 10.1038/gene.2009.66.
67. Krämer M, Dees C, Huang J, Schlottmann I, Palumbo-Zerr K, Zerr P, et al. Inhibition of H3K27 histone trimethylation activates fibroblasts and induces fibrosis. Ann Rheum Dis. 2013 Apr;72(4):614-20. doi: 10.1136/annrheumdis-2012-201615.
68. Niederer F, Ospelt C, Brentano F, Hottiger MO, Gay RE, Gay S, et al. SIRT1 overexpression in the rheumatoid arthritis synovium contributes to proinflammatory cytokine production and apoptosis resistance. Ann Rheum Dis. 2011 Oct;70(10):1866-73. doi: 10.1136/ard.2010.148957.
69. Pedre X, Mastronardi F, Bruck W, López-Rodas G, Kuhlmann T, Casaccia P. Changed histone acetylation patterns in normal-appearing white matter and early multiple sclerosis lesions. J Neurosci. 2011 Mar 2;31(9):3435-45. doi: 10.1523/JNEUROSCI.4507-10.2011. Erratum in: J Neurosci. 2011 Jun 1;31(22):8325.
70. Ma Y, Yue J, Zhang Y, Shi C, Odenwald M, Liang WG, et al. ACF7 regulates inflammatory colitis and intestinal wound response by orchestrating tight junction dynamics. Nat Commun. 2017 May 25;8:15375. doi: 10.1038/ncomms15375. Erratum in: Nat Commun. 2017 Jul 11;8:16121.
71. Barkas F, Liberopoulos E, Kei A, Elisaf M. Electrolyte and acid-base disorders in inflammatory bowel disease. Ann Gastroenterol. 2013;26(1):23-28. PMID: 24714322; PMCID: PMC3959504.
72. Dipiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM. Pharmacotherapy: A Pathophysiologic Approach, ed: McGraw-Hill Medical, New York; 2014.
73. Harris RA, Shah R, Hollister EB, Tronstad RR, Hovdenak N, Szigeti R, et al. Colonic Mucosal Epigenome and Microbiome Development in Children and Adolescents. J Immunol Res. 2016;2016:9170162. doi: 10.1155/2016/9170162.
74. Howell KJ, Kraiczy J, Nayak KM, Gasparetto M, Ross A, Lee C, et al. DNA Methylation and Transcription Patterns in Intestinal Epithelial Cells From Pediatric Patients With Inflammatory Bowel Diseases Differentiate Disease Subtypes and Associate With Outcome. Gastroenterology. 2018 Feb;154(3):585-598. doi: 10.1053/j.gastro.2017.10.007.
75. Liu Y, Peng J, Sun T, Li N, Zhang L, Ren J, et al. Epithelial EZH2 serves as an epigenetic determinant in experimental colitis by inhibiting TNFα-mediated inflammation and apoptosis. Proc Natl Acad Sci U S A. 2017 May 9;114(19):E3796-E3805. doi: 10.1073/pnas.1700909114.
76. Taman H, Fenton CG, Hensel IV, Anderssen E, Florholmen J, Paulssen RH. Genome-wide DNA Methylation in Treatment-naïve Ulcerative Colitis. J Crohns Colitis. 2018 Nov 15;12(11):1338-1347. doi: 10.1093/ecco-jcc/jjy117.
77. Barnicle A, Seoighe C, Greally JM, Golden A, Egan LJ. Inflammation-associated DNA methylation patterns in epithelium of ulcerative colitis. Epigenetics. 2017 Aug;12(8):591-606. doi: 10.1080/15592294.2017.1334023.
78. McDermott E, Ryan EJ, Tosetto M, Gibson D, Burrage J, Keegan D, et al. DNA Methylation Profiling in Inflammatory Bowel Disease Provides New Insights into Disease Pathogenesis. J Crohns Colitis. 2016 Jan;10(1):77-86. doi: 10.1093/ecco-jcc/jjv176.
79. Kumar A, Malhotra P, Coffing H, Priyamvada S, Anbazhagan AN, Krishnan HR, et al. Epigenetic modulation of intestinal Na+/H+ exchanger-3 expression. Am J Physiol Gastrointest Liver Physiol. 2018 Mar 1;314(3):G309-G318. doi: 10.1152/ajpgi.00293.2017.
80. Kelly D, Kotliar M, Woo V, Jagannathan S, Whitt J, Moncivaiz J, et al. Microbiota-sensitive epigenetic signature predicts inflammation in Crohn's disease. JCI Insight. 2018 Sep 20;3(18):e122104. doi: 10.1172/jci.insight.122104.
81. Klasić M, Markulin D, Vojta A, Samaržija I, Biruš I, Dobrinić P, et al.; IBD consortium, Lauc G, Zoldoš V. Promoter methylation of the MGAT3 and BACH2 genes correlates with the composition of the immunoglobulin G glycome in inflammatory bowel disease. Clin Epigenetics. 2018 Jun 4;10:75. doi: 10.1186/s13148-018-0507-y.
82. Khan FA, Pandupuspitasari NS, Chun-Jie H, Ao Z, Jamal M, Zohaib A, et al. CRISPR/Cas9 therapeutics: a cure for cancer and other genetic diseases. Oncotarget. 2016 Aug 9;7(32):52541-52552. doi: 10.18632/oncotarget.9646.
83. Mohan C, Putterman C. Genetics and pathogenesis of systemic lupus erythematosus and lupus nephritis. Nat Rev Nephrol. 2015 Jun;11(6):329-41. doi: 10.1038/nrneph.2015.33.
84. Gensterblum E, Renauer P, Coit P, Strickland FM, Kilian NC, Miller S, et al.. CD4+CD28+KIR+CD11ahi T cells correlate with disease activity and are characterized by a pro-inflammatory epigenetic and transcriptional profile in lupus patients. J Autoimmun. 2018 Jan;86:19-28. doi: 10.1016/j.jaut.2017.09.011.
85. Chen L, Morris DL, Vyse TJ. Genetic advances in systemic lupus erythematosus: an update. Curr Opin Rheumatol. 2017 Sep;29(5):423-433. doi: 10.1097/BOR.0000000000000411.
86. Yung R, Kaplan M, Ray D, Schneider K, Mo RR, Johnson K, Richardson B. Autoreactive murine Th1 and Th2 cells kill syngeneic macrophages and induce autoantibodies. Lupus. 2001;10(8):539-46. doi: 10.1191/096120301701549660.
87. Long H, Yin H, Wang L, Gershwin ME, Lu Q. The critical role of epigenetics in systemic lupus erythematosus and autoimmunity. J Autoimmun. 2016 Nov;74:118-138. doi: 10.1016/j.jaut.2016.06.020.
88. Ulff-Møller CJ, Asmar F, Liu Y, Svendsen AJ, Busato F, Grønbaek K, Tost J, Jacobsen S. Twin DNA Methylation Profiling Reveals Flare-Dependent Interferon Signature and B Cell Promoter Hypermethylation in Systemic Lupus Erythematosus. Arthritis Rheumatol. 2018 Jun;70(6):878-890. doi: 10.1002/art.40422.
89. Zhao H, Wang L, Luo H, Li QZ, Zuo X. TNFAIP3 downregulation mediated by histone modification contributes to T-cell dysfunction in systemic lupus erythematosus. Rheumatology (Oxford). 2017 May 1;56(5):835-843. doi: 10.1093/rheumatology/kew508.
90. Bentham J, Morris DL, Graham DSC, Pinder CL, Tombleson P, Behrens TW, et al. Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus. Nat Genet. 2015 Dec;47(12):1457-1464. doi: 10.1038/ng.3434.
91. Farh KK, Marson A, Zhu J, Kleinewietfeld M, Housley WJ, Beik S, et al. Genetic and epigenetic fine mapping of causal autoimmune disease variants. Nature. 2015 Feb 19;518(7539):337-43. doi: 10.1038/nature13835.
92. Rubin AJ, Parker KR, Satpathy AT, Qi Y, Wu B, Ong AJ, et al. Coupled Single-Cell CRISPR Screening and Epigenomic Profiling Reveals Causal Gene Regulatory Networks. Cell. 2019 Jan 10;176(1-2):361-376.e17. doi: 10.1016/j.cell.2018.11.022.
93. Coit P, Dozmorov MG, Merrill JT, McCune WJ, Maksimowicz-McKinnon K, Wren JD, Sawalha AH. Epigenetic Reprogramming in Naive CD4+ T Cells Favoring T Cell Activation and Non-Th1 Effector T Cell Immune Response as an Early Event in Lupus Flares. Arthritis Rheumatol. 2016 Sep;68(9):2200-9. doi: 10.1002/art.39720.
94. Tsou PS, Coit P, Kilian NC, Sawalha AH. EZH2 Modulates the DNA Methylome and Controls T Cell Adhesion Through Junctional Adhesion Molecule A in Lupus Patients. Arthritis Rheumatol. 2018 Jan;70(1):98-108. doi: 10.1002/art.40338.
95. Zouali M. Chapter 28—epigenetics and autoimmune diseases A2—Rose, Noel R. In: Mackay IR (ed) The autoimmune diseases. Academic Press, Boston, 2014; pp 381–401.
96. Thiagalingam S, Cheng KH, Lee HJ, Mineva N, Thiagalingam A, Ponte JF. Histone deacetylases: unique players in shaping the epigenetic histone code. Ann N Y Acad Sci. 2003 Mar;983:84-100. doi: 10.1111/j.1749-6632.2003.tb05964.x.
97. Guan KL, Xiong Y. Regulation of intermediary metabolism by protein acetylation. Trends Biochem Sci. 2011 Feb;36(2):108-16. doi: 10.1016/j.tibs.2010.09.003.
98. Xiong Y, Guan KL. Mechanistic insights into the regulation of metabolic enzymes by acetylation. J Cell Biol. 2012 Jul 23;198(2):155-64. doi: 10.1083/jcb.201202056.
Download Article
Received August 8, 2022.
Accepted September 19, 2022.
©2022 International Medical Research and Development Corporation.
