Developmental and environmental epigenetic programming of the endocrine pancreas: Consequences for type 2 diabetes

Cellular and Molecular Life Sciences

Volumn 70, Issue 9, 2013, Pages 1575-1595

  Sandovici, Ionel ^a,b   Hammerle, Constanze M ^a   Ozanne, Susan E ^a,b   Constância, Miguel ^a,b  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^b National Institute for Health Research ^*  (United Kingdom)

Author keywords

Development; Diabetes; Environment; Epigenetics; Islets; Pancreas

Indexed keywords

ACETYL COENZYME A; COENZYME A; DNA; HEPATOCYTE NUCLEAR FACTOR 4ALPHA; HEXOSAMINE; HISTONE; HISTONE METHYLTRANSFERASE; NICOTINAMIDE ADENINE DINUCLEOTIDE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE; S ADENOSYLMETHIONINE; TRANSCRIPTION FACTOR PDX 1;

AGING; BIOSYNTHESIS; CELL DIFFERENTIATION; CELL FUNCTION; CELL LINEAGE; CHROMATIN; DNA METHYLATION; ENERGY METABOLISM; ENVIRONMENTAL FACTOR; EPIGENETICS; GENE EXPRESSION; GENE INTERACTION; GENE MAPPING; GENOME ANALYSIS; HISTONE ACETYLATION; HISTONE METHYLATION; HISTONE MODIFICATION; HOMEOSTASIS; HUMAN; MOLECULAR MECHANICS; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; ORGANOGENESIS; OXIDATIVE STRESS; PANCREAS; PANCREAS ISLET BETA CELL; PATHOGENESIS; REVIEW; TRANSCRIPTION REGULATION;

ANIMALS; DIABETES MELLITUS, TYPE 2; EPIGENESIS, GENETIC; GENE EXPRESSION REGULATION, DEVELOPMENTAL; GENE-ENVIRONMENT INTERACTION; HUMANS; ISLETS OF LANGERHANS;

EID: 84876664330     PISSN: 1420682X     EISSN: 14209071     Source Type: Journal    
DOI: 10.1007/s00018-013-1297-1     Document Type: Review

References (172)

1. Shaw JE, Sicree RA, Zimmet PZ (2010) Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract 87:4-14
2. Stumvoll M, Goldstein BJ, van Haeften TW (2005) Type 2 diabetes: principles of pathogenesis and therapy. Lancet 365:1333-1346
3. Bloomgarden ZT (2004) Diabetes complications. Diabetes Care 27:1506-1514 (Pubitemid 38680004)
4. Poulsen P, Kyvik KO, Vaag A, Beck-Nielsen H (1999) Heritability of type II (non-insulin-dependent) diabetes mellitus and abnormal glucose tolerance - a population-based twin study. Diabetologia 42:139-145 (Pubitemid 29064234)
5. Doria A, Patti ME, Kahn CR (2008) The emerging genetic architecture of type 2 diabetes. Cell Metab 8:186-200
6. McCarthy MI (2010) Genomics, type 2 diabetes, and obesity. N Engl J Med 363:2339-2350
7. Bonnefond A, Froguel P, Vaxillaire M (2010) The emerging genetics of type 2 diabetes. Trends Mol Med 16:407-416
8. Zimmet P, Alberti KG, Shaw J (2001) Global and societal implications of the diabetes epidemic. Nature 414:782-787 (Pubitemid 34000780)
9. Jin W, Patti ME (2009) Genetic determinants and molecular pathways in the pathogenesis of type 2 diabetes. Clin Sci (Lond) 116:99-111
10. Jirtle RL, Skinner MK (2007) Environmental epigenomics and disease susceptibility. Nat Rev Genet 8:253-262 (Pubitemid 46439287)
11. Hochberg Z, Feil R, Constância M, Fraga M, Junien C et al (2010) Child health, developmental plasticity, and epigenetic programming. Endocr Rev 32:159-224
12. Bird A (2007) Perceptions of epigenetics. Nature 447:396-398 (Pubitemid 46816744)
13. Suzuki MM, Bird A (2008) DNA methylation landscapes: provocative insights from epigenomics. Nat Rev Genet 9:465-476 (Pubitemid 351693975)
14. Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H et al (2009) Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324:930-935
15. Ito S, Shen L, Dai Q, Wu SC, Collins LB et al (2011) Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science 333:1300-1303
16. Bannister AJ, Kouzarides T (2011) Regulation of chromatin by histone modifications. Cell Res 21:381-395
17. Talbert PB, Henikoff S (2010) Histone variants - ancient wrap artists of the epigenome. Nat Rev Mol Cell Biol 11:264-275
18. Bai L, Morozov AV (2010) Gene regulation by nucleosome positioning. Trends Genet 26:476-483
19. Ringrose L, Paro R (2004) Epigenetic regulation of cellular memory by the Polycomb and Trithorax group proteins. Annu Rev Genet 38:413-443 (Pubitemid 40013734)
20. Brenner C, Fuks F (2007) A methylation rendezvous: reader meets writers. Dev Cell 12:843-844 (Pubitemid 46805929)
21. Simon JA, Kingston RE (2009) Mechanisms of Polycomb gene silencing: knowns and unknowns. Nat Rev Mol Cell Biol 10:697-708
22. Grewal SI (2010) RNAi-dependent formation of heterochromatin and its diverse functions. Curr Opin Genet Dev 20:134-141
23. Berger SL, Kouzarides T, Shiekhattar R, Shilatifard A (2009) An operational definition of epigenetics. Genes Dev 23:781-783
24. Reik W (2007) Stability and flexibility of epigenetic gene regulation in mammalian development. Nature 447:425-432 (Pubitemid 46816749)
25. Ozanne SE, Constância M (2007) Mechanisms of disease: the developmental origins of disease and the role of the epigenotype. Nat Clin Pract Endocrinol Metab 3:539-546 (Pubitemid 46975821)
26. Gites GK (2009) Developmental biology of the pancreas: a comprehensive review. Dev Biol 326:4-35
27. Pan FC, Wright C (2011) Pancreas organogenesis: from bud to plexus to gland. Dev Dyn 240:530-565
28. Zaret KS, Grompe M (2008) Generation and regeneration of cells of the liver and pancreas. Science 322:1490-1494
29. Zaret KS (2008) Genetic programming of liver and pancreas progenitors: lessons for stem-cell differentiation. Nat Rev Genet 9:329-340 (Pubitemid 351556060)
30. Puri S, Hebrok M (2010) Cellular plasticity within the pancreas - lessons learned from development. Dev Cell 18:342-356
31. Scaglia L, Cahill CJ, Finegood DT, Bonner-Weir S (1997) Apoptosis participates in the remodeling of the endocrine pancreas in the neonatal rat. Endocrinol 138:1736-1741 (Pubitemid 27137129)
32. Bonner-Weir S, Li WC, Ouziel-Yahalom L, Guo L, Weir GC et al (2010) Beta-cell growth and regeneration: replication is only part of the story
33. Bernstein BE, Mikkelsen TS, Xie X, Kamal M, Huebert DJ et al (2006) A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125:315-326
34. Mikkelsen TS, Ku M, Jaffe DB, Issac B, Lieberman E et al (2007) Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448:553-560 (Pubitemid 47206934)
35. Xu CR, Cole PA, Meyers DJ, Kormish J, Dent S et al (2011) Chromatin "prepattern" and histone modifiers in a fate choice for liver and pancreas. Science 332:963-966
36. van Arensbergen J, García-Hurtado J, Moran I, Maestro MA, Xu X et al (2010) Derepression of Polycomb targets during pancreatic organogenesis allows insulin-producing beta-cells to adopt a neural gene activity program. Genome Res 20:722-732
37. Haumaitre C, Lenoir O, Scharfmann R (2008) Histone deacetylase inhibitors modify pancreatic cell fate determination and amplify endocrine progenitors. Mol Cell Biol 28:6373-6383
38. Lenoir O, Flosseau K, Ma FX, Blondeau B, Mai A et al (2011) Specific control of pancreatic endocrine β- and δ-cell mass by class IIa histone deacetylases HDAC4, HDAC5, and HDAC9. Diabetes 60:2861-2871
39. Rai K, Nadauld LD, Chidester S, Manos EJ, James SR et al (2006) Zebra fish Dnmt1 and Suv39h1 regulate organ-specific terminal differentiation during development. Mol Cell Biol 26:7077-7085 (Pubitemid 44477687)
40. Anderson RM, Bosch JA, Goll MG, Hesselson D, Dong PD et al (2009) Loss of Dnmt1 catalytic activity reveals multiple roles for DNA methylation during pancreas development and regeneration. Dev Biol 334:213-223
41. Dhawan S, Georgia S, Tschen SI, Fan G, Bhushan A (2011) Pancreatic β cell identity is maintained by DNA methylation-mediated repression of Arx. Dev Cell 20:419-429
42. Papizan JB, Singer RA, Tschen SI, Dhawan S, Friel JM et al (2011) Nkx2.2 repressor complex regulates islet β-cell specification and prevents β-to-α-cell reprogramming. Genes Dev 25:2291-2305
43. Chen H, Gu X, Su IH, Bottino R, Contreras JL et al (2009) Polycomb protein Ezh2 regulates pancreatic beta-cell Ink4a/Arf expression and regeneration in diabetes mellitus. Genes Dev 23:975-985
44. Deering TG, Ogihara T, Trace AP, Maier B, Mirmira RG (2009) Methyltransferase Set7/9 maintains transcription and euchromatin structure at islet-enriched genes. Diabetes 58:185-193
45. Francis J, Chakrabarti SK, Garmey JC, Mirmira RG (2005) Pdx-1 links histone H3-Lys-4 methylation to RNA polymerase II elongation during activation of insulin transcription. J Biol Chem 280:36244-36253 (Pubitemid 41633897)
46. Párrizas M, Maestro MA, Boj SF, Paniagua A, Casamitjana R et al (2001) Hepatic nuclear factor 1-alpha directs nucleosomal hyperacetylation to its tissue-specific transcriptional targets. Mol Cell Biol 21:3234-3243 (Pubitemid 32298388)
47. Luco RF, Maestro MA, Sadoni N, Zink D, Ferrer J (2008) Targeted deficiency of the transcriptional activator Hnf1alpha alters subnuclear positioning of its genomic targets. PLoS Genet 4:e1000079 (Pubitemid 351811498)
48. Kubicek S, Gilbert JC, Fomina-Yadlin D, Gitlin AD, Yuan Y et al (2012) Chromatin-targeting small molecules cause class-specific transcriptional changes in pancreatic endocrine cells. Proc Natl Acad Sci USA 109:5364-5369
49. Bhandare R, Schug J, Le Lay J, Fox A, Smirnova O et al (2010) Genome-wide analysis of histone modifications in human pancreatic islets. Genome Res 20:428-433
50. Stitzel ML, Sethupathy P, Pearson DS, Chines PS, Song L et al (2010) Global epigenomic analysis of primary human pancreatic islets provides insights into type 2 diabetes susceptibility loci. Cell Metab 12:443-455
51. Mutskov V, Felsenfeld G (2009) The human insulin gene is part of a large open chromatin domain specific for human islets. Proc Natl Acad Sci USA 106:17419-17424
52. Thorrez L, Laudadio I, Van Deun K, Quintens R, Hendrickx N et al (2011) Tissue-specific disallowance of housekeeping genes: the other face of cell differentiation. Genome Res 21:95-105
53. Gaulton KJ, Nammo T, Pasquali L, Simon JM, Giresi PG et al (2010) A map of open chromatin in human pancreatic islets. Nat Genet 42:255-259
54. Morán I, Akerman I, van de Bunt M, Xie R, Benazra M et al (2012) Human β cell transcriptome analysis uncovers lncRNAs that are tissue-specific, dynamically regulated, and abnormally expressed in type 2 diabetes. Cell Metab 16:435-448
55. Heintzman ND, Stuart RK, Hon G, Fu Y, Ching CW et al (2007) Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nat Genet 39:311-318 (Pubitemid 46328487)
56. Hoffman BG, Robertson G, Zavaglia B, Beach M, Cullum R et al (2010) Locus co-occupancy, nucleosome positioning, and H3K4me1 regulate the functionality of FOXA2-, HNF4A-, and PDX1-bound loci in islets and liver. Genome Res 20:1037-1051
57. Sekiya T, Muthurajan UM, Luger K, Tulin AV, Zaret KS (2009) Nucleosome-binding affinity as a primary determinant of the nuclear mobility of the pioneer transcription factor FoxA. Genes Dev 23:804-809
58. Thompson RF, Fazzari MJ, Niu H, Barzilai N, Simmons RA et al (2010) Experimental intrauterine growth restriction induces alterations in DNA methylation and gene expression in pancreatic islets of rats. J Biol Chem 285:15111-15118
59. Volkmar M, Dedeurwaerder S, Cunha DA, Ndlovu MN, Defrance M et al (2012) DNA methylation profiling identifies epigenetic dysregulation in pancreatic islets from type 2 diabetic patients. EMBO J 31:1405-1426
60. Xu Z, Wei G, Chepelev I, Zhao K, Felsenfeld G (2011) Mapping of INS promoter interactions reveals its role in long-range regulation of SYT8 transcription. Nat Struct Mol Biol 18:372-378
61. Sandovici I, Smith NH, Nitert MD, Ackers-Johnson M, Uribe-Lewis S et al (2011) Maternal diet and aging alter the epigenetic control of a promoter-enhancer interaction at the Hnf4a gene in rat pancreatic islets. Proc Natl Acad Sci USA 108:5449-5454
62. Bar-Nur O, Russ HA, Efrat S, Benvenisty N (2011) Epigenetic memory and preferential lineage-specific differentiation in induced pluripotent stem cells derived from human pancreatic islet Beta cells. Cell Stem Cell 9:17-23
63. Yang L, Li S, Hatch H, Ahrens K, Cornelius JG (2002) In vitro trans-differentiation of adult hepatic stem cells into pancreatic endocrine hormone-producing cells. Proc Natl Acad Sci USA 99:8078-8083 (Pubitemid 34651008)
64. Kodama S, Kühtreiber W, Fujimura S, Dale EA, Faustman DL (2003) Islet regeneration during the reversal of autoimmune diabetes in NOD mice. Science 302:1223-1227 (Pubitemid 37421029)
65. Jiang J, Au M, Lu K, Eshpeter A, Korbutt G et al (2007) Generation of insulin-producing islet-like clusters from human embryonic stem cells. Stem Cells 25:1940-1953 (Pubitemid 47258172)
66. Lumelsky N, Blondel O, Laeng P, Velasco I, Ravin R et al (2006) Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets. Science 292:1389-1394
67. Tayaramma T, Ma B, Rohde M, Mayer H (2006) Chromatin-remodeling factors allow differentiation of bone marrow cells into insulin-producing cells. Stem Cells 24:2858-2867 (Pubitemid 46053022)
68. Zhou Q, Brown J, Kanarek A, Rajagopal J, Melton DA (2008) In vivo reprogramming of adult pancreatic exocrine cells to beta-cells. Nature 455:627-632
69. Collombat P, Xu X, Ravassard P, Sosa-Pineda B, Dussaud S et al (2009) The ectopic expression of Pax4 in the mouse pancreas converts progenitor cells into alpha and subsequently beta cells. Cell 138:449-462
70. Thorel F, Népote V, Avril I, Kohno K, Desgraz R et al (2010) Conversion of adult pancreatic alpha-cells to beta-cells after extreme beta-cell loss. Nature 464:1149-1154
71. Yang YP, Thorel F, Boyer DF, Herrera PL, Wright CV (2011) Context-specific α- to-β cell reprogramming by forced Pdx1 expression. Genes Dev 25:1680-1685
72. Hales CN, Barker DJ, Clark PM, Cox LJ, Fall C et al (1991) Fetal and infant growth and impaired glucose tolerance at age 64. BMJ 303:1019-1022
73. Gluckman PD, Hanson MA, Cooper C, Thornburg KL (2008) Effect of in utero and early-life conditions on adult health and disease. N Engl J Med 359:61-73 (Pubitemid 351931097)
74. Hales CN, Barker DJ, Clark PM, Cox LJ, Fall C et al (1991) Fetal and infant growth and impaired glucose tolerance at age 64. BMJ 303:1019-1022
75. Ravelli AC, van der Meulen JH, Michels RP, Osmond C, Barker DJ et al (1998) Glucose tolerance in adults after prenatal exposure to famine. Lancet 351:173-177 (Pubitemid 28037007)
76. Remacle C, Dumortier O, Bol V, Goosse K, Romanus P et al (2007) Intrauterine programming of the endocrine pancreas. Diabetes Obes Metab 9(Suppl 2):196-209 (Pubitemid 47543142)
77. Park JH, Stoffers DA, Nicholls RD, Simmons RA (2008) Development of type 2 diabetes following intrauterine growth retardation in rats is associated with progressive epigenetic silencing of Pdx1. J Clin Invest 118:2316-2324 (Pubitemid 351872348)
78. Petry CJ, Dorling MW, Pawlak DB, Ozanne SE, Hales CN (2001) Diabetes in old male offspring of rat dams fed a reduced protein diet. Int J Exp Diabetes Res 2:139-143
79. Ng SF, Lin RC, Laybutt DR, Barres R, Owens JA et al (2010) Chronic high-fat diet in fathers programs β cell dysfunction in female rat offspring. Nature 467:963-966
80. Lillycrop KA, Phillips ES, Jackson AA, Hanson MA, Burdge GC (2005) Dietary protein restriction of pregnant rats induces and folic acid supplementation prevents epigenetic modification of hepatic gene expression in the offspring. J Nutr 135:1382-1386 (Pubitemid 40799599)
81. Suter M, Bocock P, Showalter L, Hu M, Shope C (2011) Epigenomics: maternal high-fat diet exposure in utero disrupts peripheral circadian gene expression in nonhuman primates. FASEB J 25:714-726
82. Carone BR, Fauquier L, Habib N, Shea JM, Hart CE (2011) Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals. Cell 143:1084-1096
83. Burdge GC, Lillycrop KA, Phillips ES, Slater-Jefferies JL, Jackson AA et al (2009) Folic acid supplementation during the juvenile-pubertal period in rats modifies the phenotype and epigenotype induced by prenatal nutrition. J Nutr 139:1054-1060
84. Weaver IC, Cervoni N, Champagne FA, D'Alessio AC, Sharma S et al (2004) Epigenetic programming by maternal behavior. Nat Neurosci 7:847-854 (Pubitemid 38989508)
85. Murgatroyd C, Patchev AV, Wu Y, Micale V, Bockmühl Y et al (2009) Dynamic DNA methylation programs persistent adverse effects of early-life stress. Nat Neurosci 12:1559-1566
86. Waterland RA, Jirtle RL (2003) Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol Cell Biol 23:5293-5300 (Pubitemid 36950884)
87. Ozanne SE, Sandovici I, Constância M (2011) Maternal diet, aging and diabetes meet at a chromatin loop. Aging 3:548-554
88. Chang AM, Halter JB (2003) Aging and insulin secretion. Am J Physiol Endocrinol Metab 284:E7-E12
89. Møller N, Gormsen L, Fuglsang J, Gjedsted J (2003) Effects of ageing on insulin secretion and action. Horm Res 60:102-104 (Pubitemid 37100193)
90. Iozzo P, Beck-Nielsen H, Laakso M, Smith U, Yki-Järvinen H et al (1999) Independent influence of age on basal insulin secretion in nondiabetic humans. European Group for the Study of Insulin Resistance. J Clin Endocrinol Metab 84:863-868 (Pubitemid 29138209)
91. Basu R, Breda E, Oberg AL, Powell CC, Dalla Man C et al (2003) Mechanisms of the age-associated deterioration in glucose tolerance: contribution of alterations in insulin secretion, action, and clearance. Diabetes 52:1738-1748 (Pubitemid 36792465)
92. Muzumdar R, Ma X, Atzmon G, Vuguin P, Yang X et al (2004) Decrease in glucose-stimulated insulin secretion with aging is independent of insulin action. Diabetes 53:441-446 (Pubitemid 38174561)
93. Maedler K, Schumann DM, Schulthess F, Oberholzer J, Bosco D et al (2006) Aging correlates with decreased beta-cell proliferative capacity and enhanced sensitivity to apoptosis: a potential role for Fas and pancreatic duodenal homeobox-1. Diabetes 55:2455-2462 (Pubitemid 44871145)
94. Collado M, Blasco MA, Serrano M (2007) Cellular senescence in cancer and aging. Cell 130:223-233 (Pubitemid 47081143)
95. Krishnamurthy J, Ramsey MR, Ligon KL, Torrice C, Koh A et al (2006) p16INK4a induces an age-dependent decline in islet regenerative potential. Nature 443:453-457 (Pubitemid 44477281)
96. Lee SH, Itkin-Ansari P, Levine F (2010) CENP-A, a protein required for chromosome segregation in mitosis, declines with age in islet but not exocrine cells. Aging 2:785-790
97. Tiedge M, Lortz S, Drinkgern J, Lenzen S (1997) Relation between antioxidant enzyme gene expression and antioxidative defense status of insulin-producing cells. Diabetes 46:1733-1742 (Pubitemid 27456404)
98. Kuhlow D, Florian S, von Figura G, Weimer S, Schulz N et al (2010) Telomerase deficiency impairs glucose metabolism and insulin secretion. Aging 2:650-658
99. Tarry-Adkins JL, Chen JH, Smith NS, Jones RH, Cherif H et al (2009) Poor maternal nutrition followed by accelerated postnatal growth leads to telomere shortening and increased markers of cell senescence in rat islets. FASEB J 23:1521-1528
100. Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F et al (2005) Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci USA 102:10604-10609 (Pubitemid 41061601)
101. Bjornsson HT, Sigurdsson MI, Fallin MD, Irizarry RA, Aspelund T et al (2008) Intra-individual change over time in DNA methylation with familial clustering. JAMA 299:2877-2883 (Pubitemid 351930887)
102. Christensen BC, Houseman EA, Marsit CJ, Zheng S, Wrensch MR et al (2009) Aging and environmental exposures alter tissue-specific DNA methylation dependent upon CpG island context. PLoS Genet 5:e1000602
103. Rakyan VK, Down TA, Maslau S, Andrew T, Yang TP et al (2010) Human aging-associated DNA hypermethylation occurs preferentially at bivalent chromatin domains. Genome Res 20:434-439
104. Thompson RF, Atzmon G, Gheorghe C, Liang HQ, Lowes C et al (2010) Tissue-specific dysregulation of DNA methylation in aging. Aging Cell 9:506-518
105. Grönniger E, Weber B, Heil O, Peters N, Stäb F et al (2010) Aging and chronic sun exposure cause distinct epigenetic changes in human skin. PLoS Genet 6:e1000971
106. Bocker MT, Hellwig I, Breiling A, Eckstein V, Ho AD et al (2011) Genome-wide promoter DNA methylation dynamics of human hematopoietic progenitor cells during differentiation and aging. Blood 117:e182-e189
107. Song CX, Szulwach KE, Fu Y, Dai Q, Yi C et al (2011) Selective chemical labeling reveals the genome-wide distribution of 5-hydroxymethylcytosine. Nat Biotechnol 29:68-72
108. Szulwach KE, Li X, Li Y, Song CX, Wu H et al (2011) 5-hmC-mediated epigenetic dynamics during postnatal neurodevelopment and aging. Nat Neurosci 14:1607-1616
109. Cheung I, Shulha HP, Jiang Y, Matevossian A, Wang J et al (2010) Developmental regulation and individual differences of neuronal H3K4me3 epigenomes in the prefrontal cortex. Proc Natl Acad Sci USA 107:8824-8829
110. Peleg S, Sananbenesi F, Zovoilis A, Burkhardt S, Bahari-Javan S et al (2010) Altered histone acetylation is associated with age-dependent memory impairment in mice. Science 328:753-756
111. Krishnan V, Chow MZ, Wang Z, Zhang L, Liu B et al (2011) Histone H4 lysine 16 hypoacetylation is associated with defective DNA repair and premature senescence in Zmpste24-deficient mice. Proc Natl Acad Sci USA 108:12325-31230
112. Zhang R, Poustovoitov MV, Ye X, Santos HA, Chen W et al (2005) Formation of MacroH2A-containing senescence-associated heterochromatin foci and senescence driven by ASF1a and HIRA. Dev Cell 8:19-30 (Pubitemid 40058002)
113. Narita M, Narita M, Krizhanovsky V, Nuñez S, Chicas A et al (2006) A novel role for high-mobility group a proteins in cellular senescence and heterochromatin formation. Cell 126:503-514 (Pubitemid 44163608)
114. Funayama R, Saito M, Tanobe H, Ishikawa F (2006) Loss of linker histone H1 in cellular senescence. J Cell Biol 175:869-880 (Pubitemid 44969193)
115. O'Sullivan RJ, Kubicek S, Schreiber SL, Karlseder J (2010) Reduced histone biosynthesis and chromatin changes arising from a damage signal at telomeres. Nat Struct Mol Biol 17:1218-1225
116. Chen H, Gu X, Liu Y, Wang J, Wirt SE et al (2011) PDGF signalling controls age-dependent proliferation in pancreatic β cells. Nature 478:349-355
117. Margueron R, Li G, Sarma K, Blais A, Zavadil J et al (2008) Ezh1 and Ezh2 maintain repressive chromatin through different mechanisms. Mol Cell 32:503-518
118. Rankin MM, Kushner JA (2010) Aging induces a distinct gene expression program in mouse islets. Islets 2:4-11
119. Kamiya M, Judson H, Okazaki Y, Kusakabe M, Muramatsu M et al (2000) The cell cycle control gene ZAC/PLAGL1 is imprinted - a strong candidate gene for transient neonatal diabetes. Hum Mol Genet 9:453-460 (Pubitemid 30098740)
120. Mackay DJ, Coupe AM, Shield JP, Storr JN, Temple IK et al (2002) Relaxation of imprinted expression of ZAC and HYMAI in a patient with transient neonatal diabetes mellitus. Hum Genet 110:139-144 (Pubitemid 36067430)
121. Gardner RJ, Mackay DJ, Mungall AJ, Polychronakos C, Siebert R et al (2000) An imprinted locus associated with transient neonatal diabetes mellitus. Hum Mol Genet 9:589-596 (Pubitemid 30154017)
122. Arima T, Drewell RA, Arney KL, Inoue J, Makita Y (2001) A conserved imprinting control region at the HYMAI/ZAC domain is implicated in transient neonatal diabetes mellitus. Hum Mol Genet 10:1475-1483 (Pubitemid 32684889)
123. Du X, Rousseau M, Ounissi-Benkalha H, Marchand L, Jetha A et al (2011) Differential expression pattern of ZAC in developing mouse and human pancreas. J Mol Histol 42:129-136
124. Ma D, Shield JP, Dean W, Leclerc I, Knauf C et al (2004) Impaired glucose homeostasis in transgenic mice expressing the human transient neonatal diabetes mellitus locus, TNDM. J Clin Invest 114:339-348 (Pubitemid 39071606)
125. Ling C, Del Guerra S, Lupi R, Rönn T, Granhall C et al (2008) Epigenetic regulation of PPARGC1A in human type 2 diabetic islets and effect on insulin secretion. Diabetologia 51:615-622
126. Yang BT, Dayeh TA, Kirkpatrick CL, Taneera J, Kumar R et al (2011) Insulin promoter DNA methylation correlates negatively with insulin gene expression and positively with HbA(1c) levels in human pancreatic islets. Diabetologia 54:360-367
127. Yang BT, Dayeh TA, Volkov PA, Kirkpatrick CL, Malmgren S et al (2012) Increased DNA methylation and decreased expression of PDX-1 in pancreatic islets from patients with type 2 diabetes. Mol Endocrinol 26:1203-1212
128. Kong A, Steinthorsdottir V, Masson G, Thorleifsson G, Sulem P et al (2009) Parental origin of sequence variants associated with complex diseases. Nature 462:868-874
129. Toperoff G, Aran D, Kark JD, Rosenberg M, Dubnikov T et al (2012) Genome-wide survey reveals predisposing diabetes type 2-related DNA methylation variations in human peripheral blood. Hum Mol Genet 21:371-383
130. Donohoe DR, Bultman SJ (2012) Metaboloepigenetics: Interrelationships between energy metabolism and epigenetic control of gene expression. J Cell Physiol. doi: 10.1002/jcp.24054
131. Hanover JA, Krause MW, Love DC (2012) Post-translational modifications: Bittersweet memories: linking metabolism to epigenetics through O-GlcNAcylation. Nat Rev Mol Cell Biol 13:312-321
132. Niculescu MD, Zeisel SH (2002) Diet, methyl donors and DNA methylation: interactions between dietary folate, methionine and choline. J Nutr 132:2333S-2335S (Pubitemid 34848102)
133. Turner BM (2009) Epigenetic responses to environmental change and their evolutionary implications. Philos Trans R Soc Lond B Biol Sci 364:3403-3418
134. Teperino R, Schoonjans K, Auwerx J (2010) Histone methyl transferases and demethylases; can they link metabolism and transcription? Cell Metab 12:321-327
135. Cyr AR, Domann FE (2011) The redox basis of epigenetic modifications: from mechanisms to functional consequences. Antioxid Redox Signal 15:551-589
136. Feil R, Fraga MF (2012) Epigenetics and the environment: emerging patterns and implications. Nat Rev Genet 13:97-109
137. Smith GC, Konycheva G, Dziadek MA, Ravelich SR, Patel S et al (2011) Pre- and postnatal methyl deficiency in the rat differentially alters glucose homeostasis. J Nutrigenet Nutrigenomics 4:175-191
138. Sandovici I, Smith NH, Ozanne SE, Constância M (2008) The dynamic epigenome: the impact of the environment on epigenetic regulation of gene expression and developmental programming. In: Tost J (ed) Epigenetics. Caister Academic, Norfolk, pp 343-370
139. Khulan B, Cooper WN, Skinner BM, Bauer J, Owens S et al (2012) Periconceptional maternal micronutrient supplementation is associated with widespread gender related changes in the epigenome: a study of a unique resource in the Gambia. Hum Mol Genet 21:2086-2101
140. Yu J, Auwerx J (2009) The role of sirtuins in the control of metabolic homeostasis. Ann N Y Acad Sci 1173(Suppl 1):E10-E19
141. Wellen KE, Hatzivassiliou G, Sachdeva UM, Bui TV, Cross JR et al (2009) ATP-citrate lyase links cellular metabolism to histone acetylation. Science 324:1076-1080
142. Grummt I, Ladurner AG (2008) A metabolic throttle regulates the epigenetic state of rDNA. Cell 133:577-580 (Pubitemid 351637625)
143. Guarente L (2011) The logic linking protein acetylation and metabolism. Cell Metab 14:151-153
144. Hallows WC, Lee S, Denu JM (2006) Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases. Proc Natl Acad Sci USA 103:10230-10235 (Pubitemid 44051149)
145. Nakahata Y, Sahar S, Astarita G, Kaluzova M, Sassone-Corsi P (2009) Circadian control of the NAD+ salvage pathway by CLOCK-SIRT1. Science 324:654-657
146. Katada S, Imhof A, Sassone-Corsi P (2012) Connecting threads: epigenetics and metabolism. Cell 148:24-28
147. Donohoe DR, Garge N, Zhang X, Sun W, O'Connell TM et al (2011) The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. Cell Metab 13:517-526
148. Liu HK, Green BD, Flatt PR, McClenaghan NH, McCluskey JT (2004) Effects of long-term exposure to nicotinamide and sodium butyrate on growth, viability, and the function of clonal insulin secreting cells. Endocr Res 30:61-68 (Pubitemid 38452221)
149. Vetterli L, Brun T, Giovannoni L, Bosco D, Maechler P (2011) Resveratrol potentiates glucose-stimulated insulin secretion in INS-1E beta-cells and human islets through a SIRT1-dependent mechanism. J Biol Chem 286:6049-6060
150. Zhang S, Roche K, Nasheuer HP, Lowndes NF (2011) Modification of histones by sugar β-N-acetylglucosamine (GlcNAc) occurs on multiple residues, including histone H3 serine 10, and is cell cycle-regulated. J Biol Chem 286:37483-37495
151. Fujiki R, Hashiba W, Sekine H, Yokoyama A, Chikanishi T et al (2011) GlcNAcylation of histone H2B facilitates its monoubiquitination. Nature 480:557-560
152. Gambetta MC, Oktaba K, Müller J (2009) Essential role of the glycosyltransferase sxc/Ogt in Polycomb repression. Science 325:93-96
153. Fujiki R, Chikanishi T, Hashiba W, Ito H, Takada I et al (2009) GlcNAcylation of a histone methyltransferase in retinoic-acid-induced granulopoiesis. Nature 459:455-459
154. Hanover JA, Lai Z, Lee G, Lubas WA, Sato SM (1999) Elevated O-linked N-acetylglucosamine metabolism in pancreatic beta-cells. Arch Biochem Biophys 362:38-45 (Pubitemid 29391649)
155. Liu K, Paterson AJ, Chin E, Kudlow JE (2000) Glucose stimulates protein modification by O-linked GlcNAc in pancreatic beta cells: linkage of O-linked GlcNAc to beta cell death. Proc Natl Acad Sci USA 97:2820-2825 (Pubitemid 30159255)
156. Soesanto Y, Luo B, Parker G, Jones D, Cooksey RC et al (2011) Pleiotropic and age-dependent effects of decreased protein modification by O-linked N-acetylglucosamine on pancreatic β-cell function and vascularisation. J Biol Chem 286:26118-26126
157. Lehman DM, Fu DJ, Freeman AB, Hunt KJ, Leach RJ et al (2005) A single nucleotide polymorphism in MGEA5 encoding O-GlcNAc-selective N-acetyl-beta-d glucosaminidase is associated with type 2 diabetes in Mexican Americans. Diabetes 54:1214-1221 (Pubitemid 40446339)
158. Kebede M, Ferdaoussi M, Mancini A, Alquier T, Kulkarni RN et al (2012) Glucose activates free fatty acid receptor 1 gene transcription via phosphatidylinositol-3-kinase-dependent O-GlcNAcylation of pancreas-duodenum homeobox-1. Proc Natl Acad Sci USA 109:2376-2381
159. Wisniewski JR, Zougman A, Mann M (2008) Nepsilon-formylation of lysine is a widespread post-translational modification of nuclear proteins occurring at residues involved in regulation of chromatin function. Nucleic Acids Res 36:570-577 (Pubitemid 351250448)
160. Valinluck V, Tsai HH, Rogstad DK, Burdzy A, Bird A et al (2004) Oxidative damage to methyl-CpG sequences inhibits the binding of the methyl-CpG binding domain (MBD) of methyl-CpG binding protein 2 (MeCP2). Nucleic Acids Res 32:4100-4108 (Pubitemid 39232282)
161. Yildirim O, Li R, Hung JH, Chen PB, Dong X et al (2011) Mbd3/NURD complex regulates expression of 5-hydroxymethylcytosine marked genes in embryonic stem cells. Cell 147:1498-1510
162. Bhutani N, Burns DM, Blau HM (2011) DNA demethylation dynamics. Cell 146:866-872
163. Chia N, Wang L, Lu X, Senut MC, Brenner C et al (2011) Hypothesis: environmental regulation of 5-hydroxymethylcytosine by oxidative stress. Epigenetics 6:853-856
164. Kouzarides T (2007) Chromatin modifications and their function. Cell 128:693-705 (Pubitemid 46273577)
165. Oberdoerffer P, Michan S, McVay M, Mostoslavsky R, Vann J et al (2008) SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging. Cell 135:907-918
166. Theys N, Clippe A, Bouckenooghe T, Reusens B, Remacle C (2009) Early low protein diet aggravates unbalance between antioxidant enzymes leading to islet dysfunction. PLoS One 4:e6110
167. Tarry-Adkins JL, Chen JH, Jones RH, Smith NH, Ozanne SE (2010) Poor maternal nutrition leads to alterations in oxidative stress, antioxidant defense capacity, and markers of fibrosis in rat islets: potential underlying mechanisms for development of the diabetic phenotype in later life. FASEB J 24:2762-2771
168. Dreja T, Jovanovic Z, Rasche A, Kluge R, Herwig R et al (2010) Diet-induced gene expression of isolated pancreatic islets from a polygenic mouse model of the metabolic syndrome. Diabetologia 53:309-320
169. Valle MM, Graciano MF, Lopes de Oliveira ER, Camporez JP, Akamine EH et al (2011) Alterations of NADPH oxidase activity in rat pancreatic islets induced by a high-fat diet. Pancreas 40:390-395
170. Tanaka Y, Tran PO, Harmon J, Robertson RP (2002) A role for glutathione peroxidase in protecting pancreatic beta cells against oxidative stress in a model of glucose toxicity. Proc Natl Acad Sci USA 99:12363-12368
171. Song B, Scheuner D, Ron D, Pennathur S, Kaufman RJ (2008) Chop deletion reduces oxidative stress, improves beta cell function, and promotes cell survival in multiple mouse models of diabetes. J Clin Invest 118:3378-3389
172. McDaniell R, Lee BK, Song L, Liu Z, Boyle AP et al (2010) Heritable individual-specific and allele-specific chromatin signatures in humans. Science 328:235-239