Abstract
Epigenetic mechanisms, which include DNA methylation, histone modification, and microRNA (miRNA), can produce heritable phenotypic changes without a change in DNA sequence. Disruption of gene expression patterns which are governed by epigenetics can result in autoimmune diseases, cancers, and various other maladies. Mechanisms of epigenetics include DNA methylation (and demethylation), histone modifications, and non-coding RNAs such as microRNAs. Compared to numerous studies that have focused on the field of genetics, research on epigenetics is fairly recent. In contrast to genetic changes, which are difficult to reverse, epigenetic aberrations can be pharmaceutically reversible. The emerging tools of epigenetics can be used as preventive, diagnostic, and therapeutic markers. With the development of drugs that target the specific epigenetic mechanisms involved in the regulation of gene expression, development and utilization of epigenetic tools are an appropriate and effective approach that can be clinically applied to the treatment of various diseases.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Adelman ER et al (2019) Aging human hematopoietic stem cells manifest profound epigenetic reprogramming of enhancers that may predispose to leukemia. Cancer Discov. https://doi.org/10.1158/2159-8290.cd-18-1474
Al-Hayali MA et al (2019) Clinical value of circulating microribonucleic acids miR-1 and miR-21 in evaluating the diagnosis of acute heart failure in asymptomatic type 2 diabetic patients. Biomolecules 9. https://doi.org/10.3390/biom9050193
Angiolilli C et al (2017) Histone deacetylase 3 regulates the inflammatory gene expression programme of rheumatoid arthritis fibroblast-like synoviocytes. Ann Rheum Dis 76:277–285. https://doi.org/10.1136/annrheumdis-2015-209064
Angiolilli C et al (2018) Control of cytokine mRNA degradation by the histone deacetylase inhibitor ITF2357 in rheumatoid arthritis fibroblast-like synoviocytes: beyond transcriptional regulation. Arthritis Res Ther 20:148. https://doi.org/10.1186/s13075-018-1638-4
Azghandi S et al (2015) Deficiency of the stroke relevant HDAC9 gene attenuates atherosclerosis in accord with allele-specific effects at 7p21.1. Stroke 46:197–202. https://doi.org/10.1161/strokeaha.114.007213
Bagnato G, Roberts WN, Roman J, Gangemi S (2017) A systematic review of overlapping microRNA patterns in systemic sclerosis and idiopathic pulmonary fibrosis. Eur Respir Rev: Off J Eur Respir Soc 26. https://doi.org/10.1183/16000617.0125-2016
Bailey MA (2017) 11beta-Hydroxysteroid dehydrogenases and hypertension in the metabolic syndrome. Curr Hypertens Rep 19:100. https://doi.org/10.1007/s11906-017-0797-z
Basheer F et al (2019) Contrasting requirements during disease evolution identify EZH2 as a therapeutic target in AML. J Exp Med 216:966–981. https://doi.org/10.1084/jem.20181276
Bermingham ML et al (2019) Identification of novel differentially methylated sites with potential as clinical predictors of impaired respiratory function and COPD. EBioMedicine. https://doi.org/10.1016/j.ebiom.2019.03.072
Bird A (2002) DNA methylation patterns and epigenetic memory. Genes Dev 16:6–21. https://doi.org/10.1101/gad.947102
Bocchi L et al (2019) The histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) restores cardiomyocyte contractility in a Rat model of early diabetes. Int J Mol Sci 20. https://doi.org/10.3390/ijms20081873
Bond J et al (2019) DNMT3A mutation is associated with increased age and adverse outcome in adult T-acute lymphoblastic leukemia. Haematologica. https://doi.org/10.3324/haematol.2018.197848
Bonvin E et al (2019) TET2-dependent hydroxymethylome plasticity reduces melanoma initiation and progression. Cancer Res 79:482–494. https://doi.org/10.1158/0008-5472.can-18-1214
Brocks D et al (2017) DNMT and HDAC inhibitors induce cryptic transcription start sites encoded in long terminal repeats. Nat Genet 49:1052–1060. https://doi.org/10.1038/ng.3889
Burnett A, Wetzler M, Lowenberg B (2011) Therapeutic advances in acute myeloid leukemia. J Clin Oncol: Off J Am Soc Clin Oncol 29:487–494. https://doi.org/10.1200/jco.2010.30.1820
Calin GA et al (2002) Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA 99:15524–15529. https://doi.org/10.1073/pnas.242606799
Cao Q et al (2014) Inhibiting DNA Methylation by 5-Aza-2’-deoxycytidine ameliorates atherosclerosis through suppressing macrophage inflammation. Endocrinology 155:4925–4938. https://doi.org/10.1210/en.2014-1595
Cecchinato V et al (2018) Redox-mediated mechanisms fuel monocyte responses to CXCL12/HMGB1 in active rheumatoid arthritis. Front Immunol 9:2118. https://doi.org/10.3389/fimmu.2018.02118
Chang PV, Hao L, Offermanns S, Medzhitov R (2014) The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc Natl Acad Sci USA 111:2247–2252. https://doi.org/10.1073/pnas.1322269111
Chaturvedi V et al (2003) Role of INK4a/Arf locus-encoded senescent checkpoints activated in normal and psoriatic keratinocytes. Am J Pathol 162:161–170. https://doi.org/10.1016/s0002-9440(10)63807-2
Chen YP et al (2016) DNA methylation and histone acetylation regulate the expression of MGMT and chemosensitivity to temozolomide in malignant melanoma cell lines. Tumour Biol: J Int Soc Oncodevelopmental Biol Med 37:11209–11218. https://doi.org/10.1007/s13277-016-4994-1
Chen Y et al (2019) Let-7a inhibits proliferation and promotes apoptosis of human asthmatic airway smooth muscle cells. Exp Ther Med 17:3327–3334. https://doi.org/10.3892/etm.2019.7363
Chiappella A, Santambrogio E, Castellino A, Nicolosi M, Vitolo U (2017) Integrating novel drugs to chemoimmunotherapy in diffuse large B-cell lymphoma. Exp Rev Hematol 10:697–705. https://doi.org/10.1080/17474086.2017.1350164
Choi YJ et al (2014) Frameshift mutation of a histone methylation-related gene SETD1B and its regional heterogeneity in gastric and colorectal cancers with high microsatellite instability. Hum Pathol 45:1674–1681. https://doi.org/10.1016/j.humpath.2014.04.013
Cimmino L et al (2017) Restoration of TET2 function blocks aberrant self-renewal and leukemia progression. Cell 170, 1079–1095, e1020. https://doi.org/10.1016/j.cell.2017.07.032
Coit P et al (2013) Genome-wide DNA methylation study suggests epigenetic accessibility and transcriptional poising of interferon-regulated genes in naive CD4+ T cells from lupus patients. J Autoimmun 43:78–84. https://doi.org/10.1016/j.jaut.2013.04.003
Coit P et al (2019) Genome-wide DNA methylation analysis in ankylosing spondylitis identifies HLA-B*27 dependent and independent DNA methylation changes in whole blood. J Autoimmun. https://doi.org/10.1016/j.jaut.2019.04.022
Comer BS et al (2014) MicroRNA-146a and microRNA-146b expression and anti-inflammatory function in human airway smooth muscle. Am J Physiol Lung Cell Mol Physiol 307:L727–L734. https://doi.org/10.1152/ajplung.00174.2014
Cooke J et al (2012) Mucosal genome-wide methylation changes in inflammatory bowel disease. Inflamm Bowel Dis 18:2128–2137. https://doi.org/10.1002/ibd.22942
Coppede F (2017) Epigenetics and autoimmune thyroid diseases. Front Endocrinol (Lausanne) 8:149. https://doi.org/10.3389/fendo.2017.00149
Costa-Pinheiro P, Montezuma D, Henrique R, Jeronimo C (2015) Diagnostic and prognostic epigenetic biomarkers in cancer. Epigenomics 7:1003–1015. https://doi.org/10.2217/epi.15.56
Costello JF et al (2000) Aberrant CpG-island methylation has non-random and tumour-type-specific patterns. Nat Genet 24:132–138. https://doi.org/10.1038/72785
Coward WR, Feghali-Bostwick CA, Jenkins G, Knox AJ, Pang L (2014) A central role for G9a and EZH2 in the epigenetic silencing of cyclooxygenase-2 in idiopathic pulmonary fibrosis. FASEB J: Off Publ Fed Am Soc Exp Biol 28:3183–3196. https://doi.org/10.1096/fj.13-241760
Cronin JC et al (2018) Identification and functional analysis of SOX10 phosphorylation sites in melanoma. PloS One 13:e0190834. https://doi.org/10.1371/journal.pone.0190834
da Costa Martins PA et al (2010) MicroRNA-199b targets the nuclear kinase Dyrk1a in an auto-amplification loop promoting calcineurin/NFAT signalling. Nat Cell Biol 12:1220–1227. https://doi.org/10.1038/ncb2126
Davies ER et al (2012) Spiruchostatin A inhibits proliferation and differentiation of fibroblasts from patients with pulmonary fibrosis. Am J Respir Cell Mol Biol 46:687–694. https://doi.org/10.1165/rcmb.2011-0040OC
Dees C et al (2014) The Wnt antagonists DKK1 and SFRP1 are downregulated by promoter hypermethylation in systemic sclerosis. Ann Rheum Dis 73:1232–1239. https://doi.org/10.1136/annrheumdis-2012-203194
Del Vescovo V, Denti MA (2015) microRNA and Lung Cancer. Adv Exp Med Biol 889:153–177. https://doi.org/10.1007/978-3-319-23730-5_9
Deng C et al (2003) Hydralazine may induce autoimmunity by inhibiting extracellular signal-regulated kinase pathway signaling. Arthritis Rheum 48:746–756. https://doi.org/10.1002/art.10833
Deng Z et al (2017) MicroRNA-29: a crucial player in fibrotic disease. Mol Diagn Ther 21:285–294. https://doi.org/10.1007/s40291-016-0253-9
Dirks RA, Stunnenberg HG, Marks H (2016) Genome-wide epigenomic profiling for biomarker discovery. Clinical epigenetics 8:122. https://doi.org/10.1186/s13148-016-0284-4
Donaldson SS, Laningham F, Fisher PG (2006) Advances toward an understanding of brainstem gliomas. J Clin Oncol: Off J Am Soc Clin Oncol 24:1266–1272. https://doi.org/10.1200/jco.2005.04.6599
Drogan D, Schulze MB, Boeing H, Pischon T (2016) Insulin-like growth factor 1 and Insulin-like growth factor-binding protein 3 in relation to the risk of type 2 diabetes mellitus: results from the EPIC-potsdam study. Am J Epidemiol 183:553–560. https://doi.org/10.1093/aje/kwv188
Du C et al (2009) MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis. Nat Immunol 10:1252–1259. https://doi.org/10.1038/ni.1798
Dunaeva M, Blom J, Thurlings R, Pruijn GJM (2018) Circulating serum miR-223-3p and miR-16-5p as possible biomarkers of early rheumatoid arthritis. Clin Exp Immunol 193:376–385. https://doi.org/10.1111/cei.13156
Egger G, Liang G, Aparicio A, Jones PA (2004) Epigenetics in human disease and prospects for epigenetic therapy. Nature 429:457–463. https://doi.org/10.1038/nature02625
Esteller M (2007) Cancer epigenomics: DNA methylomes and histone-modification maps. Nat Rev Genet 8:286–298. https://doi.org/10.1038/nrg2005
Esteller M (2008) Epigenetics in evolution and disease. The Lancet 372:S90–S96. https://doi.org/10.1016/S0140-6736(08)61887-5
Evans LW, Ferguson BS (2018) Food bioactive HDAC inhibitors in the epigenetic regulation of heart failure. Nutrients 10. https://doi.org/10.3390/nu10081120
Ezzat S, Yu S, Asa SL (2003) Ikaros isoforms in human pituitary tumors: distinct localization, histone acetylation, and activation of the 5′ fibroblast growth factor receptor-4 promoter. Am J Pathol 163:1177–1184. https://doi.org/10.1016/s0002-9440(10)63477-3
Fan X et al (2019) Abnormal expression of SIRTs in psoriasis: decreased expression of SIRT 1-5 and increased expression of SIRT 6 and 7. Int J Mol Med. https://doi.org/10.3892/ijmm.2019.4173
Fang J et al (2018) Cancer-driving H3G34V/R/D mutations block H3K36 methylation and H3K36me3-MutSalpha interaction. Proc Natl Acad Sci USA 115:9598–9603. https://doi.org/10.1073/pnas.1806355115
Faraco G, Cavone L, Chiarugi A (2011) The therapeutic potential of HDAC inhibitors in the treatment of multiple sclerosis. Mol Med (Cambridge, MA) 17:442–447. https://doi.org/10.2119/molmed.2011.00077
Felice C, Lewis A, Armuzzi A, Lindsay JO, Silver A (2015) Review article: selective histone deacetylase isoforms as potential therapeutic targets in inflammatory bowel diseases. Aliment Pharmacol Ther 41:26–38. https://doi.org/10.1111/apt.13008
Fraga MF et al (2005) Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci USA 102:10604–10609. https://doi.org/10.1073/pnas.0500398102
Garcia-Gimenez JL et al (2017a) Epigenetic biomarkers: current strategies and future challenges for their use in the clinical laboratory. Crit Rev Clin Lab Sci 54:529–550. https://doi.org/10.1080/10408363.2017.1410520
Garcia-Gimenez JL, Mena-Molla S, Beltran-Garcia J, Sanchis-Gomar F (2017b) Challenges in the analysis of epigenetic biomarkers in clinical samples. Clin Chem Lab Med 55:1474–1477. https://doi.org/10.1515/cclm-2016-1162
Gardner EE et al (2017) Chemosensitive relapse in small cell lung cancer proceeds through an EZH2-SLFN11 axis. Cancer Cell 31:286–299. https://doi.org/10.1016/j.ccell.2017.01.006
Garzon R et al (2009) MicroRNA 29b functions in acute myeloid leukemia. Blood 114:5331–5341. https://doi.org/10.1182/blood-2009-03-211938
Gilbane AJ et al (2015) Impaired bone morphogenetic protein receptor II signaling in a transforming growth factor-beta-dependent mouse model of pulmonary hypertension and in systemic sclerosis. Am J Respir Crit Care Med 191:665–677. https://doi.org/10.1164/rccm.201408-1464OC
Giri AK, Aittokallio T (2019) DNMT inhibitors increase methylation in the cancer genome. Front Pharmacol 10:385. https://doi.org/10.3389/fphar.2019.00385
Grasso CS et al (2015) Functionally defined therapeutic targets in diffuse intrinsic pontine glioma. Nat Med 21:555–559. https://doi.org/10.1038/nm.3855
Guo M, Yan W (2015) Epigenetics of gastric cancer. Methods Mol Biol 1238:783–799. https://doi.org/10.1007/978-1-4939-1804-1_41
Guo Q et al (2018) Alterations of global DNA Methylation and DNA Methyltransferase expression in T and B Lymphocytes from patients with newly diagnosed autoimmune thyroid diseases after treatment: a follow-up study. Thyroid: Off J Am Thyroid Assoc 28:377–385. https://doi.org/10.1089/thy.2017.0301
Han X, Zheng Z, Wang C, Wang L (2018) Association between MEG3/miR-181b polymorphisms and risk of ischemic stroke. Lipids Health Dis 17:292. https://doi.org/10.1186/s12944-018-0941-z
Han L et al (2016) DNA methylation and hypertension: emerging evidence and challenges. Brief Funct Genomics 15:460–469. https://doi.org/10.1093/bfgp/elw014
Hawkes JE et al (2016) microRNAs in Psoriasis. J Investig Derm 136:365–371. https://doi.org/10.1038/jid.2015.409
Hedrich CM, Rauen T (2012) Epigenetic patterns in systemic sclerosis and their contribution to attenuated CD70 signaling cascades. Clin Immunol 143:1–3. https://doi.org/10.1016/j.clim.2012.01.017
Heijink IH et al (2016) Cigarette smoke-induced epithelial expression of WNT-5B: implications for COPD. Eur Respir J 48:504–515. https://doi.org/10.1183/13993003.01541-2015
Holliday R, Pugh JE (1975) DNA modification mechanisms and gene activity during development. Science 187:226–232
Izutsu K et al (2001) The corepressor CtBP interacts with Evi-1 to repress transforming growth factor beta signaling. Blood 97:2815–2822
Javierre BM et al (2010) Changes in the pattern of DNA methylation associate with twin discordance in systemic lupus erythematosus. Genome Res 20:170–179. https://doi.org/10.1101/gr.100289.109
Jiang Y et al (2015) Histone H3K9 demethylase JMJD1A modulates hepatic stellate cells activation and liver fibrosis by epigenetically regulating peroxisome proliferator-activated receptor gamma. FASEB J: Off Publ Fed Am Soc Exp Biol 29:1830–1841. https://doi.org/10.1096/fj.14-251751
Jones PA (2012) Functions of DNA methylation: Islands, start sites, gene bodies and beyond. Nat Rev Genet 13:484–492. https://doi.org/10.1038/nrg3230
Jones PA, Baylin SB (2002) The fundamental role of epigenetic events in cancer. Nat Rev Genet 3:415–428. https://doi.org/10.1038/nrg816
Kacerovsky-Bielesz G et al (2009) Short-term exercise training does not stimulate skeletal muscle ATP synthesis in relatives of humans with type 2 diabetes. Diabetes 58:1333–1341. https://doi.org/10.2337/db08-1240
Kaminsky ZA et al (2009) DNA methylation profiles in monozygotic and dizygotic twins. Nat Genet 41:240–245. https://doi.org/10.1038/ng.286
Khaleva E et al (2019) Transforming growth factor beta in human milk and allergic outcomes in children: a systematic review. Clin Exp Allergy: J Br Soc Allergy Clin Immunol. https://doi.org/10.1111/cea.13409
Khan S, Ahirwar K, Jena G (2016) Anti-fibrotic effects of valproic acid: role of HDAC inhibition and associated mechanisms. Epigenomics 8:1087–1101. https://doi.org/10.2217/epi-2016-0034
KhorshidAhmad T et al (2016) Transcriptional regulation of brain-derived neurotrophic factor (BDNF) by Methyl CpG Binding Protein 2 (MeCP2): a novel mechanism for re-myelination and/or myelin repair involved in the treatment of multiple sclerosis (MS). Mol Neurobiol 53:1092–1107. https://doi.org/10.1007/s12035-014-9074-1
Khoshmirsafa M et al (2019) Elevated expression of miR-21 and miR-155 in peripheral blood mononuclear cells as potential biomarkers for lupus nephritis. Int J Rheum Dis 22:458–467. https://doi.org/10.1111/1756-185x.13410
Kodama S et al (2018) Quantitative relationship between cumulative risk alleles based on genome-wide association studies and type 2 diabetes mellitus: a systematic review and meta-analysis. J Epidemiol 28:3–18. https://doi.org/10.2188/jea.JE20160151
Korfei M et al (2018) Comparison of the antifibrotic effects of the pan-histone deacetylase-inhibitor panobinostat versus the IPF-drug pirfenidone in fibroblasts from patients with idiopathic pulmonary fibrosis. PLoS One 13:e0207915. https://doi.org/10.1371/journal.pone.0207915
Laffont B, Rayner KJ (2017) MicroRNAs in the pathobiology and therapy of atherosclerosis. Can J Cardiol 33:313–324. https://doi.org/10.1016/j.cjca.2017.01.001
Lai T et al (2018) HDAC2 suppresses IL17A-mediated airway remodeling in human and experimental modeling of COPD. Chest 153:863–875. https://doi.org/10.1016/j.chest.2017.10.031
Lavallee VP et al (2016) Chemo-genomic interrogation of CEBPA mutated AML reveals recurrent CSF3R mutations and subgroup sensitivity to JAK inhibitors. Blood 127:3054–3061. https://doi.org/10.1182/blood-2016-03-705053
Lee HA et al (2018) Histone deacetylase inhibition ameliorates hypertension and hyperglycemia in a model of Cushing’s syndrome. Am J Physiol Endocrinol Metab 314:E39–E52. https://doi.org/10.1152/ajpendo.00267.2017
Leone V et al (2014) Mir-23b and miR-130b expression is downregulated in pituitary adenomas. Mol Cell Endocrinol 390:1–7. https://doi.org/10.1016/j.mce.2014.03.002
Li X (2014) MiR-375, a microRNA related to diabetes. Gene 533:1–4. https://doi.org/10.1016/j.gene.2013.09.105
Li P, Yang QZ, Wang W, Zhang GQ, Yang J (2018) Increased IL-4- and IL-17-producing CD8(+) cells are related to decreased CD39(+)CD4(+)Foxp3(+) cells in allergic asthma. J Asthma: Off J Assoc Care Asthma 55:8–14. https://doi.org/10.1080/02770903.2017.1310225
Li H et al (2006) Genetic polymorphisms in arginase I and II and childhood asthma and atopy. J Allergy Clin Immunol 117:119–126. https://doi.org/10.1016/j.jaci.2005.09.026
Li RF et al (2017a) Roles of HDAC2 and HDAC8 in cardiac remodeling in renovascular hypertensive rats and the effects of valproic acid sodium. Pharmacology 99:27–39. https://doi.org/10.1159/000449467
Li B et al (2017b) The blood genome-wide DNA methylation analysis reveals novel epigenetic changes in human heart failure. European review for medical and pharmacological sciences 21:1828–1836
Li C et al (2019) A novel CDKN2A variant (p16(L117P)) in a patient with familial and multiple primary melanomas. Pigment Cell Melanoma Res. https://doi.org/10.1111/pcmr.12787
Liang G, Weisenberger DJ (2017) DNA methylation aberrancies as a guide for surveillance and treatment of human cancers. Epigenetics 1–17. https://doi.org/10.1080/15592294.2017.1311434
Liu S et al (2005) Interplay of RUNX1/MTG8 and DNA methyltransferase 1 in acute myeloid leukemia. Can Res 65:1277–1284. https://doi.org/10.1158/0008-5472.can-04-4532
Liu Y et al (2019) Role of microRNAs, circRNAs and long noncoding RNAs in acute myeloid leukemia. J Hematol Oncol 12:51. https://doi.org/10.1186/s13045-019-0734-5
Lombard DB, Cierpicki T, Grembecka J (2019) Combined MAPK pathway and HDAC inhibition breaks melanoma. Cancer Discov 9:469–471. https://doi.org/10.1158/2159-8290.cd-19-0069
Lorincz AT (2011) The promise and the problems of epigenetics biomarkers in cancer. Exp Opin Med Diagn 5:375–379. https://doi.org/10.1517/17530059.2011.590129
Lu Q et al (2002) Demethylation of ITGAL (CD11a) regulatory sequences in systemic lupus erythematosus. Arthritis Rheum 46:1282–1291. https://doi.org/10.1002/art.10234
Lu Q et al (2007) Demethylation of CD40LG on the Inactive X in T Cells from women with lupus. J Immunol 179:6352–6358. https://doi.org/10.4049/jimmunol.179.9.6352
Maeda M, Moro H, Ushijima T (2017) Mechanisms for the induction of gastric cancer by Helicobacter pylori infection: aberrant DNA methylation pathway. Gastric Cancer 20:8–15. https://doi.org/10.1007/s10120-016-0650-0
Maekita T et al (2006) High levels of aberrant DNA methylation in Helicobacter pylori-infected gastric mucosae and its possible association with gastric cancer risk. Clin Cancer Res: Off J Am Assoc Cancer Res 12:989–995. https://doi.org/10.1158/1078-0432.ccr-05-2096
Malhotra D et al (2008) Decline in NRF2-regulated antioxidants in chronic obstructive pulmonary disease lungs due to loss of its positive regulator, DJ-1. Am J Respir Crit Care Med 178:592–604. https://doi.org/10.1164/rccm.200803-380OC
Mao R et al (2010) Association study between methylenetetrahydrofolate reductase gene polymorphisms and Graves’ disease. Cell Biochem Funct 28:585–590. https://doi.org/10.1002/cbf.1694
McDermott E et al (2016) DNA methylation profiling in inflammatory bowel disease provides new insights into disease pathogenesis. J Crohn’s & Colitis 10:77–86. https://doi.org/10.1093/ecco-jcc/jjv176
Meissner A et al (2008) Genome-scale DNA methylation maps of pluripotent and differentiated cells. Nature 454:766–770. https://doi.org/10.1038/nature07107
Milosevic J et al (2012) Profibrotic role of miR-154 in pulmonary fibrosis. Am J Respir Cell Mol Biol 47:879–887. https://doi.org/10.1165/rcmb.2011-0377OC
Mishra N, Reilly CM, Brown DR, Ruiz P, Gilkeson GS (2003) Histone deacetylase inhibitors modulate renal disease in the MRL-lpr/lpr mouse. J Clin Investig 111:539–552. https://doi.org/10.1172/jci16153
Miyazaki T et al (2007) E-cadherin gene promoter hypermethylation in H. pylori-induced enlarged fold gastritis. Helicobacter 12:523–531. https://doi.org/10.1111/j.1523-5378.2007.00519.x
Mizuno S et al (2001) Expression of DNA methyltransferases DNMT1, 3A, and 3B in normal hematopoiesis and in acute and chronic myelogenous leukemia. Blood 97:1172–1179
Mizuno K et al (2017) MicroRNAs in non-small cell lung cancer and idiopathic pulmonary fibrosis. J Hum Genet 62:57–65. https://doi.org/10.1038/jhg.2016.98
Moein S et al (2019) MiRNAs and inflammatory bowel disease: an interesting new story. J Cell Physiol 234:3277–3293. https://doi.org/10.1002/jcp.27173
Mohammad F et al (2017) EZH2 is a potential therapeutic target for H3K27M-mutant pediatric gliomas. Nat Med 23:483–492. https://doi.org/10.1038/nm.4293
Morente MM, Fernandez PL, de Alava E (2008) Biobanking: old activity or young discipline? Semin Diagn Pathol 25:317–322
Morera L, Lubbert M, Jung M (2016) Targeting histone methyltransferases and demethylases in clinical trials for cancer therapy. Clinical epigenetics 8:57. https://doi.org/10.1186/s13148-016-0223-4
Nagaraja S et al (2017) Transcriptional dependencies in diffuse intrinsic pontine glioma. Cancer Cell 31:635–652, e636. https://doi.org/10.1016/j.ccell.2017.03.011
Nakashima T et al (2012) Impaired IL-17 signaling pathway contributes to the increased collagen expression in scleroderma fibroblasts. J Immunol 188:3573–3583. https://doi.org/10.4049/jimmunol.1100591
Nakayama J, Rice JC, Strahl BD, Allis CD, Grewal SI (2001) Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly. Science 292:110–113. https://doi.org/10.1126/science.1060118
Necula LG, Mambet C, Albulescu R, Diaconu CC (2015) Epigenetics in gastric carcinogenesis: TET genes as important players. J Immunoass Immunochem 36:445–455. https://doi.org/10.1080/15321819.2015.1017402
Nemecz M, Alexandru N, Tanko G, Georgescu A (2016) Role of MicroRNA in endothelial dysfunction and hypertension. Curr Hypertens Rep 18:87. https://doi.org/10.1007/s11906-016-0696-8
Nemeth K et al (2019) Comprehensive analysis of circulating microRNAs in plasma of patients with pituitary adenomas. J Clin Endocrinol Metab. https://doi.org/10.1210/jc.2018-02479
Ni Y et al (2018) Gene set enrichment analysis: a genome-wide expression profile-based strategy for discovering functional microRNA-disease relationships. J Int Med Res 46:596–611. https://doi.org/10.1177/0300060517693719
Nuhrenberg TG et al (2015) Cardiac Myocyte De Novo DNA methyltransferases 3a/3b are dispensable for cardiac function and remodeling after chronic pressure overload in mice. PloS One 10:e0131019. https://doi.org/10.1371/journal.pone.0131019
Oelke K et al (2004) Overexpression of CD70 and overstimulation of IgG synthesis by lupus T cells and T cells treated with DNA methylation inhibitors. Arthritis Rheum 50:1850–1860. https://doi.org/10.1002/art.20255
Oh BK et al (2007) DNA methyltransferase expression and DNA methylation in human hepatocellular carcinoma and their clinicopathological correlation. Int J Mol Med 20:65–73
Organista-Nava J et al (2015) High miR-24 expression is associated with risk of relapse and poor survival in acute leukemia. Oncol Rep 33:1639–1649. https://doi.org/10.3892/or.2015.3787
Ouimet M et al (2017) microRNA-33 regulates macrophage autophagy in atherosclerosis. Arter Thromb Vasc Biol 37:1058–1067. https://doi.org/10.1161/atvbaha.116.308916
Pandit KV et al (2010) Inhibition and role of let-7d in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 182:220–229. https://doi.org/10.1164/rccm.200911-1698OC
Pang M, Zhuang S (2010) Histone deacetylase: a potential therapeutic target for fibrotic disorders. J Pharmacol Exp Ther 335:266–272. https://doi.org/10.1124/jpet.110.168385
Pang JC, Kwok WK, Chen Z, Ng HK (2009) Oncogenic role of microRNAs in brain tumors. Acta Neuropathol 117:599–611. https://doi.org/10.1007/s00401-009-0525-0
Pelosi A et al (2013) miRNA let-7c promotes granulocytic differentiation in acute myeloid leukemia. Oncogene 32:3648–3654. https://doi.org/10.1038/onc.2012.398
Portela A, Esteller M (2010) Epigenetic modifications and human disease. Nat Biotechnol 28:1057–1068. https://doi.org/10.1038/nbt.1685
Powles RL et al (1980) The place of bone-marrow transplantation in acute myelogenous leukaemia. Lancet (London, England) 1:1047–1050
Qin Q et al (2015) Aberrant expression of miRNA and mRNAs in lesioned tissues of Graves’ disease. Cell Physiol Biochem: Int J Exp Cell Physiol, Biochem, Pharmacol 35:1934–1942. https://doi.org/10.1159/000374002
Qiu J et al (2018) Notch promotes DNMT-mediated hypermethylation of Klotho leads to COPD-related inflammation. Exp Lung Res 44:368–377. https://doi.org/10.1080/01902148.2018.1556749
Riddick G, Fine HA (2011) Integration and analysis of genome-scale data from gliomas. Nat Rev Neurol 7:439–450. https://doi.org/10.1038/nrneurol.2011.100
Rideout WM 3rd, Eggan K, Jaenisch R (2001) Nuclear cloning and epigenetic reprogramming of the genome. Science 293:1093–1098. https://doi.org/10.1126/science.1063206
Riggs AD (1975) X inactivation, differentiation, and DNA methylation. Cytogenet Cell Genet 14:9–25. https://doi.org/10.1159/000130315
Romano G, Kwong LN (2017) miRNAs, melanoma and microenvironment: an intricate network. Int J Mol Sci 18. https://doi.org/10.3390/ijms18112354
Roper J, Sheng X (2019) Novel patient-derived cultures of patient-derived cancer and tumor immune cells. Gastroenterology. https://doi.org/10.1053/j.gastro.2019.05.036
Roulois D et al (2015) DNA-Demethylating agents target colorectal cancer cells by inducing viral mimicry by endogenous transcripts. Cell 162:961–973. https://doi.org/10.1016/j.cell.2015.07.056
Royce SG, Karagiannis TC (2014) Histone deacetylases and their inhibitors: new implications for asthma and chronic respiratory conditions. Curr Opin Allergy Clin Immunol 14:44–48. https://doi.org/10.1097/aci.0000000000000029
Ruchusatsawat K, Wongpiyabovorn J, Shuangshoti S, Hirankarn N, Mutirangura A (2006) SHP-1 promoter 2 methylation in normal epithelial tissues and demethylation in psoriasis. J Mol Med (Berlin, Germany) 84:175–182. https://doi.org/10.1007/s00109-005-0020-6
Russler-Germain DA et al (2014) The R882H DNMT3A mutation associated with AML dominantly inhibits wild-type DNMT3A by blocking its ability to form active tetramers. Cancer Cell 25:442–454. https://doi.org/10.1016/j.ccr.2014.02.010
Sanders YY et al (2012) Altered DNA methylation profile in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 186:525–535. https://doi.org/10.1164/rccm.201201-0077OC
Santenard A et al (2010) Heterochromatin formation in the mouse embryo requires critical residues of the histone variant H3.3. Nat Cell Biol 12:853–862. https://doi.org/10.1038/ncb2089
Sarumaru M et al (2016) Association between functional SIRT1 polymorphisms and the clinical characteristics of patients with autoimmune thyroid disease. Autoimmunity 49:329–337. https://doi.org/10.3109/08916934.2015.1134506
Schotta G et al (2004) A silencing pathway to induce H3-K9 and H4-K20 trimethylation at constitutive heterochromatin. Genes Dev 18:1251–1262. https://doi.org/10.1101/gad.300704
Schwartzentruber J et al (2012) Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature 482:226–231. https://doi.org/10.1038/nature10833
Shlush LI et al (2014) Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia. Nature 506:328–333. https://doi.org/10.1038/nature13038
Sinha S et al (2015) Mutant WT1 is associated with DNA hypermethylation of PRC2 targets in AML and responds to EZH2 inhibition. Blood 125:316–326. https://doi.org/10.1182/blood-2014-03-566018
Soroosh A, Koutsioumpa M, Pothoulakis C, Iliopoulos D (2018) Functional role and therapeutic targeting of microRNAs in inflammatory bowel disease. Am J Physiol Gastrointest Liver Physiol 314:G256–G262. https://doi.org/10.1152/ajpgi.00268.2017
Starlinger P, Pereyra D, Hackl M, Assinger A (2019) miRNA signatures in cirrhotic patients. Hepatology. https://doi.org/10.1002/hep.30682
Sun L et al (2018a) Loss of HDAC11 ameliorates clinical symptoms in a multiple sclerosis mouse model. Life Sci Alliance 1:e201800039. https://doi.org/10.26508/lsa.201800039
Sun X et al (2018b) Nucleosides isolated from ophiocordyceps sinensis inhibit cigarette smoke extract-induced inflammation via the SIRT1-nuclear factor-kappaB/p 65 pathway in RAW264.7 macrophages and in COPD mice. Int J Chronic Obstr Pulm Dis 13:2821–2832. https://doi.org/10.2147/copd.s172579
Sundar IK, Rashid K, Gerloff J, Li D, Rahman I (2018) Genetic ablation of p16(INK4a) does not protect against cellular senescence in mouse models of chronic obstructive pulmonary disease/emphysema. Am J Respir Cell Mol Biol 59:189–199. https://doi.org/10.1165/rcmb.2017-0390OC
Syreeni A et al (2011) Genetic examination of SETD7 and SUV39H1/H2 methyltransferases and the risk of diabetes complications in patients with type 1 diabetes. Diabetes 60:3073–3080. https://doi.org/10.2337/db11-0073
Szczyrek M et al (2019) Diagnostic value of plasma expression of microRNAs complementary to Drosha and Dicer in lung cancer patients. Eur Rev Med Pharmacol Sci 23:3857–3866. https://doi.org/10.26355/eurrev_201905_17813
Szymczak I, Wieczfinska J, Pawliczak R (2016) Molecular background of miRNA role in asthma and COPD: an updated insight. Biomed Res Int 2016:7802521. https://doi.org/10.1155/2016/7802521
Tabaei S, Tabaee SS (2019) DNA methylation abnormalities in atherosclerosis. Artif Cells Nanomed Biotechnol 47:2031–2041. https://doi.org/10.1080/21691401.2019.1617724
Tanemura A et al (2009) CpG island methylator phenotype predicts progression of malignant melanoma. Clin Cancer Res: Off J Am Assoc Cancer Res 15:1801–1807. https://doi.org/10.1158/1078-0432.ccr-08-1361
Tang Y et al (2019) DNA hydroxymethylation changes in response to spinal cord damage in a multiple sclerosis mouse model. Epigenomics 11:323–335. https://doi.org/10.2217/epi-2018-0162
Taylor KR et al (2014) Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma. Nat Genet 46:457–461. https://doi.org/10.1038/ng.2925
Teixeira VH et al (2019) Deciphering the genomic, epigenomic, and transcriptomic landscapes of pre-invasive lung cancer lesions. Nat Med 25:517–525. https://doi.org/10.1038/s41591-018-0323-0
Tsuru Y et al (2014) miR-424 levels in hair shaft are increased in psoriatic patients. J Derm 41:382–385. https://doi.org/10.1111/1346-8138.12460
Tufarelli C et al (2003) Transcription of antisense RNA leading to gene silencing and methylation as a novel cause of human genetic disease. Nat Genet 34:157–165. https://doi.org/10.1038/ng1157
Tzilas V et al (2019) Vitamin D prevents experimental lung fibrosis and predicts survival in patients with idiopathic pulmonary fibrosis. Pulm Pharmacol Ther 55:17–24. https://doi.org/10.1016/j.pupt.2019.01.003
Urabe Y et al (2013) A genome-wide association study of HCV-induced liver cirrhosis in the Japanese population identifies novel susceptibility loci at the MHC region. J Hepatol 58:875–882. https://doi.org/10.1016/j.jhep.2012.12.024
Vegter EL, van der Meer P, de Windt LJ, Pinto YM, Voors AA (2016) MicroRNAs in heart failure: from biomarker to target for therapy. Eur J Heart Fail 18:457–468. https://doi.org/10.1002/ejhf.495
Vojinovic J et al (2011) Safety and efficacy of an oral histone deacetylase inhibitor in systemic-onset juvenile idiopathic arthritis. Arthritis Rheum 63:1452–1458. https://doi.org/10.1002/art.30238
Waddington CH (1939) An introduction to modern genetics/by C. H. Waddington. George Allen & Unwin, London
Wang Z, Heid B, Dai R, Ahmed SA (2018) Similar dyregulation of lupus-associated miRNAs in peripheral blood mononuclear cells and splenic lymphocytes in MRL/lpr mice. Lupus Sci Med 5:e000290. https://doi.org/10.1136/lupus-2018-000290
Wang QX, Zhu YQ, Zhang H, Xiao J (2015) Altered MiRNA expression in gastric cancer: a systematic review and meta-analysis. Cell Physiol Biochem: Int J Exp Cell Physiol, Biochem, Pharmacol 35:933–944. https://doi.org/10.1159/000369750
Wang Y et al (2013) Aberrant histone modification in peripheral blood B cells from patients with systemic sclerosis. Clin Immunol 149:46–54. https://doi.org/10.1016/j.clim.2013.06.006
Wang YS et al (2017) Let-7 g suppresses both canonical and non-canonical NF-kappaB pathways in macrophages leading to anti-atherosclerosis. Oncotarget 8:101026–101041. https://doi.org/10.18632/oncotarget.18197
Wierda RJ et al (2015) Global histone H3 lysine 27 triple methylation levels are reduced in vessels with advanced atherosclerotic plaques. Life Sci 129:3–9. https://doi.org/10.1016/j.lfs.2014.10.010
Wierzbicka-Tutka I et al (2016) PTTG and Ki-67 expression in pituitary adenomas. Przegl Lek 73:53–58
Wu B, Miller D (2017) Involvement of MicroRNAs in diabetes and its complications. Methods Mol Biol 1617:225–239. https://doi.org/10.1007/978-1-4939-7046-9_17
Wu G et al (2012) Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat Genet 44:251–253. https://doi.org/10.1038/ng.1102
Wu R et al (2018) MicroRNA-210 overexpression promotes psoriasis-like inflammation by inducing Th1 and Th17 cell differentiation. J Clin Invest 128:2551–2568. https://doi.org/10.1172/jci97426
Wu J et al (2019) Inhibition of P53/miR-34a improves diabetic endothelial dysfunction via activation of SIRT1. J Cell Mol Med 23:3538–3548. https://doi.org/10.1111/jcmm.14253
Yacqub-Usman K, Richardson A, Duong CV, Clayton RN, Farrell WE (2012a) The pituitary tumour epigenome: aberrations and prospects for targeted therapy. Nat Rev Endocrinol 8:486–494. https://doi.org/10.1038/nrendo.2012.54
Yacqub-Usman K, Duong CV, Clayton RN, Farrell WE (2012b) Epigenomic silencing of the BMP-4 gene in pituitary adenomas: a potential target for epidrug-induced re-expression. Endocrinology 153:3603–3612. https://doi.org/10.1210/en.2012-1231
Yalcinkaya Y et al (2016) Capillaroscopic findings and vascular biomarkers in systemic sclerosis: association of low CD40L levels with late scleroderma pattern. Microvasc Res 108:17–21. https://doi.org/10.1016/j.mvr.2016.07.002
Yan S, Yim LY, Lu L, Lau CS, Chan VS (2014) MicroRNA regulation in systemic lupus erythematosus pathogenesis. Immune Netw 14:138–148. https://doi.org/10.4110/in.2014.14.3.138
Yang X, Wu Y, Zhang B, Ni B (2018) Noncoding RNAs in multiple sclerosis. Clin Epigenetics 10. https://doi.org/10.1186/s13148-018-0586-9
Yao X et al (2017) Analysis of Ki67, HMGA1, MDM2, and RB expression in nonfunctioning pituitary adenomas. J Neurooncol 132:199–206. https://doi.org/10.1007/s11060-016-2365-9
Yoon S et al (2018) PP2A negatively regulates the hypertrophic response by dephosphorylating HDAC2 S394 in the heart. Exper Mol Med 50:83. https://doi.org/10.1038/s12276-018-0121-2
Yu Q et al (2012) DNA methyltransferase 3a limits the expression of interleukin-13 in T helper 2 cells and allergic airway inflammation. Proc Natl Acad Sci USA 109:541–546. https://doi.org/10.1073/pnas.1103803109
Yuan Y et al (2019) MicroRNA-126 affects cell apoptosis, proliferation, cell cycle and modulates VEGF/TGF-beta levels in pulmonary artery endothelial cells. Eur Rev Med Pharmacol Sci 23:3058–3069. https://doi.org/10.26355/eurrev_201904_17588
Yuen BT, Knoepfler PS (2013) Histone H3.3 mutations: a variant path to cancer. Cancer Cell 24:567–574. https://doi.org/10.1016/j.ccr.2013.09.015
Zhang X, Li Y, Qi P, Ma Z (2018) Biology of MiR-17-92 cluster and its progress in Lung Cancer. Int J Med Sci 15:1443–1448. https://doi.org/10.7150/ijms.27341
Zhang P, Su Y, Chen H, Zhao M, Lu Q (2010) Abnormal DNA methylation in skin lesions and PBMCs of patients with psoriasis vulgaris. J Dermatol Sci 60:40–42. https://doi.org/10.1016/j.jdermsci.2010.07.011
Zhang P, Su Y, Zhao M, Huang W, Lu Q (2011a) Abnormal histone modifications in PBMCs from patients with psoriasis vulgaris. Eur J Dermatol EJD 21:552–557. https://doi.org/10.1684/ejd.2011.1383
Zhang QJ et al (2011b) The histone trimethyllysine demethylase JMJD2A promotes cardiac hypertrophy in response to hypertrophic stimuli in mice. J Clin Invest 121:2447–2456. https://doi.org/10.1172/jci46277
Zheng XX, Zhou T, Wang XA, Tong XH, Ding JW (2015) Histone deacetylases and atherosclerosis. Atherosclerosis 240:355–366. https://doi.org/10.1016/j.atherosclerosis.2014.12.048
Zheng L, Zhuang C, Wang X, Ming L (2018a) Serum miR-146a, miR-155, and miR-210 as potential markers of Graves’ disease. J Clin Lab Anal 32. https://doi.org/10.1002/jcla.22266
Zheng Y et al (2018b) The miR-31-SOX10 axis regulates tumor growth and chemotherapy resistance of melanoma via PI3K/AKT pathway. Biochem Biophys Res Commun 503:2451–2458. https://doi.org/10.1016/j.bbrc.2018.06.175
Zhu Z et al (2019) miR-106b promotes metastasis of early gastric cancer by targeting ALEX1 in vitro and in vivo. Cell Physiol Biochem: Int J Exp Cell Physiol, Biochem, Pharmacol 52:606–616. https://doi.org/10.33594/000000043
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2020 Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Zhang, L., Lu, Q., Chang, C. (2020). Epigenetics in Health and Disease. In: Chang, C., Lu, Q. (eds) Epigenetics in Allergy and Autoimmunity. Advances in Experimental Medicine and Biology, vol 1253. Springer, Singapore. https://doi.org/10.1007/978-981-15-3449-2_1
Download citation
DOI: https://doi.org/10.1007/978-981-15-3449-2_1
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-15-3448-5
Online ISBN: 978-981-15-3449-2
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)