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Chromatin modifications in metabolic disease: Potential mediators of long‐term disease risk

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Kevin R. Costello, Dustin E. Schones

Published Online: Jan 25 2018

DOI: 10.1002/wsbm.1416

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Metabolic diseases such as obesity and diabetes are complex diseases resulting from multiple genetic and environmental factors, such as diet and activity levels. These factors are well known contributors to the development of metabolic diseases. One manner by which environmental factors can influence metabolic disease progression is through modifications to chromatin. These modifications can lead to altered gene regulatory programs, which alters disease risk. Furthermore, there is evidence that parents exposed to environmental factors can influence the metabolic health of offspring, especially if exposures are during intrauterine growth periods. In this review, we outline the evidence that chromatin modifications are associated with metabolic diseases, including diabetes and obesity. We also consider evidence that these chromatin modifications can lead to long‐term disease risk and contribute to disease risk for future generations. This article is categorized under: Biological Mechanisms > Metabolism Developmental Biology > Developmental Processes in Health and Disease Physiology > Organismal Responses to Environment

Chromatin modifications associated with “permissive” or “repressive” environments. Modifications to histone tails and DNA methylation are associated with “repressive” states with condensed chromatin or “permissive” state of more accessible chromatin. Red balls, DNA methylation; purple balls, repressive histone modifications; green balls, active histone modifications; yellow globes, histone proteins; blue globes, histone variants

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Small RNA‐mediated regulation of gene expression from parental small RNA. Parental small RNAs, in a function independent of the genomic information in sperm, have been shown to transmit phenotypes to offspring. sRNAs can complex to RNA transcripts and induce degradation. Alternatively, sRNAs could bind to actively transcribed RNA in the genome and cause the recruitment of DNA and histone modifying proteins. This could lead to targeted heterochromatin formation in the genome

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Intergenerational versus transgenerational inheritance. Epigenetic inheritance in mice can be defined by the number of generations the phenotype penetrates. Maternal effects are changes to the offspring caused as a result of changes in the womb, that is, starvation or altered metabolite intake. The children born after these conditions with altered epigenetic structure are the F0 generation. The F0 generation can also be generated if there is some altering effect, that is, obesogenic diet, that alter the germs cells of an individual. If the phenotype is successfully passed on from the F0 generation to their offspring, the F1 generation, the phenotype is viewed as an intergenerational phenotype. If the phenotype is successfully transferred from the F1 generation to the F2 generation and beyond, the phenotype is viewed as a transgenerational phenotype

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Epigenetics and metabolic memory. The phenomenon of metabolic memory is the observation that complications due to metabolic disease can persist even after metabolic disease is mitigated. Epigenetic modifications are an attractive candidate for mediating this phenomenon

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Metabolites and chromatin structure. Metabolites are required by many chromatin modifying proteins. S‐adenosyl methionine (SAM) is required by DNA methyltransferases (DNMTs), as well as histone methyltransferases (HMTs) to add a methyl group to DNA or histone tails (Rea et al., ). The metabolites fumartate, succinate and α‐ketogluterate regulate Ten‐eleven translocase (TET) proteins (Klose, Kallin, & Zhang, ). TETs are responsible for the removal of methyl groups from DNA. Flavin adenine dinucleotide (FAD) regulates lysine demethylase (KDM) to regulate the removal of methyl groups from histones. Acetyl‐CoA is required for the addition of acetyl groups to histones by histone acetyl transferases (HATs) (Galdieri & Vancura, ). Nicotinamide adenine dinucleotide (NADH) interacts with Sirtuins to facilitate acetyl group removal by histone deacetylases (HDACs) (Ions et al., ). ATP is a required substrate for serine/threonine kinase (ATM) phosphorylation of histones (Banerjee, Bennion, Goldberg, & Allen, ), which is removed by protein serine/threonine phosphatases (PSPs)

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Developmental epigenetic reprograming. There are waves of genome‐wide demethylation followed by the establishment of methylation in primordial germ cells (PGCs) and following fertilization. The vast majority of the genome undergoes this loss of methylation. However, a group of evolutionarily young transposable elements, referred to as “escapees,” avoid the demethylation

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References

Ahima,, R. S. (2009). Connecting obesity, aging and diabetes. Nature Medicine, 15(9), 996–997. https://doi.org/10.1038/nm0909-996
Anderson,, J. W., Konz,, E. C., Frederich,, R. C., & Wood,, C. L. (2001). Long‐term weight‐loss maintenance: A meta‐analysis of US studies. American Journal of Clinical Nutrition, 74(5), 579–584.
Banerjee,, S., Bennion,, G. R., Goldberg,, M. W., & Allen,, T. D. (1991). ATP dependent histone phosphorylation and nucleosome assembly in a human cell free extract. Nucleic Acids Research, 19(21), 5999–6006.
Bannister,, A. J., & Kouzarides,, T. (2011). Regulation of chromatin by histone modifications. Cell Research, 21(3), 381–395. https://doi.org/10.1038/cr.2011.22
Bestor,, T. H. (2000). The DNA methyltransferases of mammals. Human Molecular Genetics, 9(16), 2395–2402.
Carmell,, M. A., Girard,, A., van de Kant,, H. J., Bourc`his,, D., Bestor,, T. H., de Rooij,, R. G., & Hannon,, G. J. (2007). MIWI2 is essential for spermatogenesis and repression of transposons in the mouse male germline. Developmental Cell, 12(4), 503–514. https://doi.org/10.1016/j.devcel.2007.03.001
Chen,, Q., Yan,, M., Cao,, Z., Li,, X., Zhang,, Y., Shi,, J., … Zhou,, Q. (2016). Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder. Science, 351(6271), 397–400. https://doi.org/10.1126/science.aad7977
Clapier,, C. R., Iwasa,, J., Cairns,, B. R., & Peterson,, C. L. (2017). Mechanisms of action and regulation of ATP‐dependent chromatin‐remodelling complexes. Nature Reviews. Molecular Cell Biology, 18(7), 407–422. https://doi.org/10.1038/nrm.2017.26
Claussnitzer,, M., Dankel,, S. N., Kim,, K.‐H., Quon,, G., Meuleman,, W., Haugen,, C., … Kellis,, M. (2015). FTO obesity variant circuitry and adipocyte browning in humans. New England Journal of Medicine, 373(10), 895–907. https://doi.org/10.1056/NEJMoa1502214
Cohen,, H. Y., Miller,, C., Bitterman,, K. J., Wall,, N. R., Hekking,, B., Kessler,, B., … Sinclair,, D. A. (2004). Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science, 305(5682), 390–392. https://doi.org/10.1126/science.1099196
Cole,, J. J., Robertson,, N. A., Rather,, M. I., Thomson,, J. P., McBryan,, T., Sproul,, D., … Adams,, P. D. (2017). Diverse interventions that extend mouse lifespan suppress shared age‐associated epigenetic changes at critical gene regulatory regions. Genome Biology, 18, 58. https://doi.org/10.1186/s13059-017-1185-3
Collins,, S., Martin,, T. L., Surwit,, R. S., & Robidoux,, J. (2004). Genetic vulnerability to diet‐induced obesity in the C57BL/6J mouse: Physiological and molecular characteristics. Physiology %26 Behavior, 81(2), 243–248. https://doi.org/10.1016/j.physbeh.2004.02.006
Colman,, R. J., Beasley,, T. M., Kemnitz,, J. W., Johnson,, S. C., Weindruch,, R., & Anderson,, R. M. (2014). Caloric restriction reduces age‐related and all‐cause mortality in rhesus monkeys. Nature Communications, 5, 3557. https://doi.org/10.1038/ncomms4557
Cropley,, J. E., Eaton,, S. A., Aiken,, A., Young,, P. E., Giannoulatou,, E. H., Joshua,, W. K., … Suter,, C. M. (2016). Male‐lineage transmission of an acquired metabolic phenotype induced by grand‐paternal obesity. Molecular Metabolism, 5(8), 699–708. https://doi.org/10.1016/j.molmet.2016.06.008
Dai,, J., Wang,, Z., Xu,, W., Zhang,, M., Zhu,, Z., Zhao,, X., … Qiao,, Z. (2017). Paternal nicotine exposure defines different behavior in subsequent generation via hyper‐methylation of mmu‐miR‐15b. Scientific Reports, 7(1), 7286. https://doi.org/10.1038/s41598-017-07920-3
Dalgaard,, K., Landgraf,, K., Heyne,, S., Lempradl,, A., Longinotto,, J., Gossens,, K., … Pospisilik,, J. A. (2016). Trim28 haploinsufficiency triggers bi‐stable epigenetic obesity. Cell, 164(3), 353–364. https://doi.org/10.1016/j.cell.2015.12.025
de Assis,, S., Warri,, A., Cruz,, M. I., Laja,, O., Tian,, Y., Zhang,, B., … Hilakivi‐Clarke,, L. (2012). High‐fat or ethinyl‐oestradiol intake during pregnancy increases mammary cancer risk in several generations of offspring. Nature Communications, 3, 1053. https://doi.org/10.1038/ncomms2058
Delmas,, V., Stokes,, D. G., & Perry,, R. P. (1993). A mammalian DNA‐binding protein that contains a chromodomain and an SNF2/SWI2‐like helicase domain. Proceedings of the National Academy of Sciences of the United States of America, 90(6), 2414–2418.
Dhahbi,, J. M., Spindler,, S. R., Atamna,, H., Yamakawa,, A., Boffelli,, D., Mote,, P., & Martin,, D. I. K. (2013). 5′ tRNA halves are present as abundant complexes in serum, concentrated in blood cells, and modulated by aging and calorie restriction. BMC Genomics, 14, 298–298. https://doi.org/10.1186/1471-2164-14-298
Dolinoy,, D. C., Das,, R., Weidman,, J. R., & Jirtle,, R. L. (2007). Metastable epialleles, imprinting, and the fetal origins of adult diseases. Pediatric Research, 61(5 Part 2), 30R–37R. https://doi.org/10.1203/pdr.0b013e31804575f7
Donkin,, I., Versteyhe,, S., Ingerslev,, L. R., Qian,, K., Mechta,, M., Nordkap,, L., … Barres,, R. (2016). Obesity and bariatric surgery drive epigenetic variation of spermatozoa in humans. Cell Metabolism, 23(2), 369–378. https://doi.org/10.1016/j.cmet.2015.11.004
Du,, Z., Sun,, T., Hacisuleyman,, E., Fei,, T., Wang,, X., Brown,, M., … Liu,, X. S. (2016). Integrative analyses reveal a long noncoding RNA‐mediated sponge regulatory network in prostate cancer. Nature Communications, 7, 10982. https://doi.org/10.1038/ncomms10982
Edwards,, J. R., Yarychkivska,, O., Boulard,, M., & Bestor,, T. H. (2017). DNA methylation and DNA methyltransferases. Epigenetics %26 Chromatin, 10, 23. https://doi.org/10.1186/s13072‐017‐0130‐8
Friedman,, J. M. (2009). Obesity: Causes and control of excess body fat. Nature, 459(7245), 340–342. https://doi.org/10.1038/459340a
Galdieri,, L., & Vancura,, A. (2012). Acetyl‐CoA carboxylase regulates global histone acetylation. Journal of Biological Chemistry, 287(28), 23865–23876. https://doi.org/10.1074/jbc.M112.380519
Gao,, Y., Wu,, F., Zhou,, J., Yan,, L., Jurczak,, M. J., Lee,, H. Y., … Huang,, Y. (2014). The H19/let‐7 double‐negative feedback loop contributes to glucose metabolism in muscle cells. Nucleic Acids Research, 42(22), 13799–13811. https://doi.org/10.1093/nar/gku1160
Gluckman,, P. D., Hanson,, M. A., & Beedle,, A. S. (2007). Non‐genomic transgenerational inheritance of disease risk. BioEssays, 29(2), 145–154. https://doi.org/10.1002/bies.20522
Goll,, M. G., Kirpekar,, F., Maggert,, K. A., Yoder,, J. A., Hsieh,, C. L., Zhang,, X., … Bestor,, T. H. (2006). Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2. Science, 311(5759), 395–398. https://doi.org/10.1126/science.1120976
Green,, C. D., Huang,, Y., Dou,, X., Yang,, L., Liu,, Y., & Han,, J.‐D. J. (2017). Impact of dietary interventions on noncoding RNA networks and mRNAs encoding chromatin‐related factors. Cell Reports, 18(12), 2957–2968. https://doi.org/10.1016/j.celrep.2017.03.001
Guo,, J., Jou,, W., Gavrilova,, O., & Hall,, K. D. (2009). Persistent diet‐induced obesity in male C57BL/6 mice resulting from temporary obesigenic diets. PLoS One, 4(4), e5370. https://doi.org/10.1371/journal.pone.0005370
Hackett,, J. A., Sengupta,, R., Zylicz,, J. J., Murakami,, K., Lee,, C., Down,, T. A., & Surani,, M. A. (2013). Germline DNA demethylation dynamics and imprint erasure through 5‐hydroxymethylcytosine. Science, 339(6118), 448–452. https://doi.org/10.1126/science.1229277
Hales,, C. N., & Barker,, D. J. (1992). Type 2 (non‐insulin‐dependent) diabetes mellitus: The thrifty phenotype hypothesis. Diabetologia, 35(7), 595–601.
Harris,, R. A., Nagy‐Szakal,, D., & Kellermayer,, R. (2013). Human metastable epiallele candidates link to common disorders. Epigenetics, 8(2), 157–163. https://doi.org/10.4161/epi.23438
Hata,, K., Okano,, M., Lei,, H., & Li,, E. (2002). Dnmt3L cooperates with the Dnmt3 family of de novo DNA methyltransferases to establish maternal imprints in mice. Development, 129(8), 1983–1993.
Hawkins,, P. G., Santoso,, S., Adams,, C., Anest,, V., & Morris,, K. V. (2009). Promoter targeted small RNAs induce long‐term transcriptional gene silencing in human cells. Nucleic Acids Research, 37(9), 2984–2995. https://doi.org/10.1093/nar/gkp127
Hochberg,, Z., Feil,, R., Constancia,, M., Fraga,, M., Junien,, C., Carel,, J. C., … Albertsson‐Wikland,, K. (2011). Child health, developmental plasticity, and epigenetic programming. Endocrine Reviews, 32(2), 159–224. https://doi.org/10.1210/er.2009-0039
Holliday,, R., & Pugh,, J. E. (1975). DNA modification mechanisms and gene activity during development. Science, 187(4173), 226–232.
Horvath,, S. (2013). DNA methylation age of human tissues and cell types. Genome Biology, 14(10), R115. https://doi.org/10.1186/gb-2013-14-10-r115
Ions,, L. J., Wakeling,, L. A., Bosomworth,, H. J., Hardyman,, J. E., Escolme,, S. M., Swan,, D. C., … Ford,, D. (2013). Effects of Sirt1 on DNA methylation and expression of genes affected by dietary restriction. Age (Dordrecht, Netherlands), 35(5), 1835–1849. https://doi.org/10.1007/s11357-012-9485-8
Ito,, S., Shen,, L., Dai,, Q., Wu,, S. C., Collins,, L. B., Swenberg,, J. A., … Zhang,, Y. (2011). Tet proteins can convert 5‐methylcytosine to 5‐formylcytosine and 5‐carboxylcytosine. Science, 333(6047), 1300–1303. https://doi.org/10.1126/science.1210597
Ja,, W. W., Carvalho,, G. B., Zid,, B. M., Mak,, E. M., Brummel,, T., & Benzer,, S. (2009). Water‐ and nutrient‐dependent effects of dietary restriction on Drosophila lifespan. Proceedings of the National Academy of Sciences, 106(44), 18633–18637. https://doi.org/10.1073/pnas.0908016106
Jang,, C.‐W., Shibata,, Y., Starmer,, J., Yee,, D., & Magnuson,, T. (2015). Histone H3.3 maintains genome integrity during mammalian development. Genes %26 Development, 29(13), 1377–1392. https://doi.org/10.1101/gad.264150.115
Jin,, B., & Robertson,, K. D. (2013). DNA methyltransferases (DNMTs), DNA damage repair, and cancer. Advances in Experimental Medicine and Biology, 754, 3–29. https://doi.org/10.1007/978-1-4419-9967-2_1
Jin,, C., & Felsenfeld,, G. (2007). Nucleosome stability mediated by histone variants H3.3 and H2A.Z. Genes %26 Development, 21(12), 1519–1529. https://doi.org/10.1101/gad.1547707
Jin,, C., Zang,, C., Wei,, G., Cui,, K., Peng,, W., Zhao,, K., & Felsenfeld,, G. (2009). H3.3/H2A.Z double variant‐containing nucleosomes mark ‘nucleosome‐free regions’ of active promoters and other regulatory regions. Nature Genetics, 41(8), 941–945. https://doi.org/10.1038/ng.409
Keating,, S. T., & El‐Osta,, A. (2015). Epigenetics and metabolism. Circulation Research, 116(4), 715–736. https://doi.org/10.1161/CIRCRESAHA.116.303936
Khalil,, H., Tazi,, M., Caution,, K., Ahmed,, A., Kanneganti,, A., Assani,, K., … Amer,, A. O. (2016). Aging is associated with hypermethylation of autophagy genes in macrophages. Epigenetics, 11(5), 381–388. https://doi.org/10.1080/15592294.2016.1144007
Khodarahmi,, M., & Azadbakht,, L. (2014). The association between different kinds of fat intake and breast cancer risk in women. International Journal of Preventive Medicine, 5(1), 6–15.
Kiani,, J., Grandjean,, V., Liebers,, R., Tuorto,, F., Ghanbarian,, H., Lyko,, F., … Rassoulzadegan,, M. (2013). RNA‐mediated epigenetic heredity requires the cytosine methyltransferase Dnmt2. PLoS Genetics, 9(5), e1003498. https://doi.org/10.1371/journal.pgen.1003498
Klose,, R. J., Kallin,, E. M., & Zhang,, Y. (2006). JmjC‐domain‐containing proteins and histone demethylation. Nature Reviews Genetics, 7(9), 715–727.
Kramer,, F. M., Jeffery,, R. W., Forster,, J. L., & Snell,, M. K. (1989). Long‐term follow‐up of behavioral treatment for obesity: Patterns of weight regain among men and women. International Journal of Obesity, 13(2), 123–136.
Kühnen,, P., Handke,, D., Waterland,, R. A., Hennig,, B. J., Silver,, M., Fulford,, A. J., … Krude,, H. (2016). Interindividual variation in DNA methylation at a putative POMC metastable epiallele is associated with obesity. Cell Metabolism, 24(3), 502–509. https://doi.org/10.1016/j.cmet.2016.08.001
Kumar,, P., Kuscu,, C., & Dutta,, A. (2016). Biogenesis and function of transfer RNA‐related fragments (tRFs). Trends in Biochemical Sciences, 41(8), 679–689. https://doi.org/10.1016/j.tibs.2016.05.004
Lakowski,, B., & Hekimi,, S. (1998). The genetics of caloric restriction in Caenorhabditis elegans. Proceedings of the National Academy of Sciences of the United States of America, 95(22), 13091–13096.
Lam,, D. D., de Souza,, F. S., Nasif,, S., Yamashita,, M., Lopez‐Leal,, R., Otero‐Corchon,, V., … Low,, M. J. (2015). Partially redundant enhancers cooperatively maintain mammalian pomc expression above a critical functional threshold. PLoS Genetics, 11(2), e1004935. https://doi.org/10.1371/journal.pgen.1004935
Lane,, N., Dean,, W., Erhardt,, S., Hajkova,, P., Surani,, A., Walter,, J., & Reik,, W. (2003). Resistance of IAPs to methylation reprogramming may provide a mechanism for epigenetic inheritance in the mouse. Genesis (New York), 35(2), 88–93. https://doi.org/10.1002/gene.10168
Lappalainen,, T., & Greally,, J. M. (2017). Associating cellular epigenetic models with human phenotypes. Nature Reviews Genetics, 18(7), 441–451. https://doi.org/10.1038/nrg.2017.32
Lee,, Y. S., Shibata,, Y., Malhotra,, A., & Dutta,, A. (2009). A novel class of small RNAs: tRNA‐derived RNA fragments (tRFs). Genes %26 Development, 23(22), 2639–2649. https://doi.org/10.1101/gad.1837609
Leung,, A., Parks,, B. W., Du,, J., Trac,, C., Setten,, R., Chen,, Y., … Schones,, D. E. (2014). Open chromatin profiling in mice livers reveals unique chromatin variations induced by high fat diet. Journal of Biological Chemistry, 289(34), 23557–23567. https://doi.org/10.1074/jbc.M114.581439
Leung,, A., Trac,, C., Du,, J., Natarajan,, R., & Schones,, D. E. (2016). Persistent chromatin modifications induced by high fat diet. Journal of Biological Chemistry, 291(20), 10446–10455. https://doi.org/10.1074/jbc.M115.711028
Li,, S., Todor,, A., & Luo,, R. (2016). Blood transcriptomics and metabolomics for personalized medicine. Computational and Structural Biotechnology Journal, 14, 1–7. https://doi.org/10.1016/j.csbj.2015.10.005
Lister,, N., Shevchenko,, G., Walshe,, J. L., Groen,, J., Johnsson,, P., Vidarsdóttir,, L., … Morris,, K. V. (2017). The molecular dynamics of long noncoding RNA control of transcription in PTEN and its pseudogene. Proceedings of the National Academy of Sciences, 114(37), 9942–9947. https://doi.org/10.1073/pnas.1621490114
Lumey,, L. H., Stein,, A. D., Kahn,, H. S., van der Pal‐de Bruin,, K. M., Blauw,, G. J., Zybert,, P. A., & Susser,, E. S. (2007). Cohort profile: The Dutch Hunger Winter Families Study. International Journal of Epidemiology, 36(6), 1196–1204. https://doi.org/10.1093/ije/dym126
Mattison,, J. A., Roth,, G. S., Beasley,, T. M., Tilmont,, E. M., Handy,, A. M., Herbert,, R. L., … de Cabo,, R. (2012). Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature, 489(7415), 318–321. https://doi.org/10.1038/nature11432
McMillen,, I. C., & Robinson,, J. S. (2005). Developmental origins of the metabolic syndrome: Prediction, plasticity, and programming. Physiological Reviews, 85(2), 571–633. https://doi.org/10.1152/physrev.00053.2003
Mercer,, T. R., & Mattick,, J. S. (2013). Structure and function of long noncoding RNAs in epigenetic regulation. Nature Structural %26 Molecular Biology, 20, 300–307. https://doi.org/10.1038/nsmb.2480
Multhaup,, M. L., Seldin,, M. M., Jaffe,, A. E., Lei,, X., Kirchner,, H., Mondal,, P., … Feinberg,, A. P. (2015). Mouse‐human experimental epigenetic analysis unmasks dietary targets and genetic liability for diabetic phenotypes. Cell Metabolism, 21(1), 138–149. https://doi.org/10.1016/j.cmet.2014.12.014
Münzel,, M., Globisch,, D., Brückl,, T., Wagner,, M., Welzmiller,, V., Michalakis,, S., … Carell,, T. (2010). Quantification of the sixth DNA base hydroxymethylcytosine in the brain. Angewandte Chemie International Edition, 49(31), 5375–5377. https://doi.org/10.1002/anie.201002033
Neigeborn,, L., & Carlson,, M. (1984). Genes affecting the regulation of gene expression by glucose repression in Saccharomyces cerevisiae. Genetics, 108(4), 845–858.
O`Leary,, V. B., Hain,, S., Maugg,, D., Smida,, J., Azimzadeh,, O., Tapio,, S., … Atkinson,, M. J. (2017). Long non‐coding RNA particle bridges histone and DNA methylation. Scientific Reports, 7(1), 1790. https://doi.org/10.1038/s41598-017-01875-1
Okano,, M., Bell,, D. W., Haber,, D. A., & Li,, E. (1999). DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell, 99(3), 247–257.
Petry,, C. J., Evans,, M. L., Wingate,, D. L., Ong,, K. K., Reik,, W., Constancia,, M., & Dunger,, D. B. (2010). Raised late pregnancy glucose concentrations in mice carrying pups with targeted disruption of H19delta13. Diabetes, 59(1), 282–286. https://doi.org/10.2337/db09-0757
Portela,, A., & Esteller,, M. (2010). Epigenetic modifications and human disease. Nature Biotechnology, 28(10), 1057–1068. https://doi.org/10.1038/nbt.1685
Ptashne,, M. (2007). On the use of the word ‘epigenetic’. Current Biology, 17(7), R233–R236. https://doi.org/10.1016/j.cub.2007.02.030
Qi,, Y., Zhu,, Q., Zhang,, K., Thomas,, C., Wu,, Y., Kumar,, R., … Guo,, S. (2015). Activation of Foxo1 by insulin resistance promotes cardiac dysfunction and β‐myosin heavy chain gene expression. Circulation: Heart Failure, 8(1), 198–208. https://doi.org/10.1161/circheartfailure.114.001457
Rakyan,, V. K., Blewitt,, M. E., Druker,, R., Preis,, J. I., & Whitelaw,, E. (2002). Metastable epialleles in mammals. Trends in Genetics, 18(7), 348–351. https://doi.org/10.1016/S0168-9525(02)02709-9
Rasool,, M., Malik,, A., Naseer,, M. I., Manan,, A., Ansari,, S. A., Begum,, I., … Gan,, S. H. (2015). The role of epigenetics in personalized medicine: Challenges and opportunities. BMC Medical Genomics, 8(Suppl. 1), S1–S5. https://doi.org/10.1186/1755-8794-8-S1-S5
Rea,, S., Eisenhaber,, F., O`Carroll,, D., Strahl,, B. D., Sun,, Z. W., Schmid,, M., … Jenuwein,, T. (2000). Regulation of chromatin structure by site‐specific histone H3 methyltransferases. Nature, 406(6796), 593–599. https://doi.org/10.1038/35020506
Riggs,, A. D. (1975). X inactivation, differentiation, and DNA methylation. Cytogenetics and Cell Genetics, 14(1), 9–25.
Riggs,, A. D., Martienssen,, R. A., & Russo,, V. E. A. (1996). Introduction. In Epigenetic mechanisms of gene regulation (pp. 1–4). Cold Spring Harbour, NY: Cold Spring Harbor Laboratory Press.
Rosenbaum,, M., Hirsch,, J., Gallagher,, D. A., & Leibel,, R. L. (2008). Long‐term persistence of adaptive thermogenesis in subjects who have maintained a reduced body weight. American Journal of Clinical Nutrition, 88(4), 906–912.
Schorn,, A. J., Gutbrod,, M. J., LeBlanc,, C., & Martienssen,, R. (2017). LTR‐retrotransposon control by tRNA‐derived small RNAs. Cell, 170(1), 61–71.e11. https://doi.org/10.1016/j.cell.2017.06.013
Seisenberger,, S., Andrews,, S., Krueger,, F., Arand,, J., Walter,, J., Santos,, F., … Reik,, W. (2012). The dynamics of genome‐wide DNA methylation reprogramming in mouse primordial germ cells. Molecular Cell, 48(6), 849–862. https://doi.org/10.1016/j.molcel.2012.11.001
Sharma,, U., Conine,, C. C., Shea,, J. M., Boskovic,, A., Derr,, A. G., Bing,, X. Y., … Rando,, O. J. (2016). Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals. Science, 351(6271), 391–396. https://doi.org/10.1126/science.aad6780
Shen,, X., Mizuguchi,, G., Hamiche,, A., & Wu,, C. (2000). A chromatin remodelling complex involved in transcription and DNA processing. Nature, 406(6795), 541–544. https://doi.org/10.1038/35020123
Shibutani,, T., Ito,, S., Toda,, M., Kanao,, R., Collins,, L. B., Shibata,, M., … Kuraoka,, I. (2014). Guanine‐ 5‐carboxylcytosine base pairs mimic mismatches during DNA replication. Scientific Reports, 4, 5220. https://doi.org/10.1038/srep05220
Siersbaek,, M., Varticovski,, L., Yang,, S., Baek,, S., Nielsen,, R., Mandrup,, S., … Grontved,, L. (2017). High fat diet‐induced changes of mouse hepatic transcription and enhancer activity can be reversed by subsequent weight loss. Scientific Reports, 7, 40220. https://doi.org/10.1038/srep40220
Stubbs,, T. M., Bonder,, M. J., Stark,, A.‐K., Krueger,, F., von Meyenn,, F., Stegle,, O., & Reik,, W. (2017). Multi‐tissue DNA methylation age predictor in mouse. Genome Biology, 18(1), 68. https://doi.org/10.1186/s13059-017-1203-5
Sumithran,, P., Prendergast,, L. A., Delbridge,, E., Purcell,, K., Shulkes,, A., Kriketos,, A., & Proietto,, J. (2011). Long‐term persistence of hormonal adaptations to weight loss. The New England Journal of Medicine, 365(17), 1597–1604. https://doi.org/10.1056/NEJMoa1105816
Sun,, X., & Wong,, D. (2016). Long non‐coding RNA‐mediated regulation of glucose homeostasis and diabetes. American Journal of Cardiovascular Disease, 6(2), 17–25.
Tanaka,, M., Yasuoka,, A., Shimizu,, M., Saito,, Y., Kumakura,, K., Asakura,, T., & Nagai,, T. (2017). Transcriptomic responses of the liver and adipose tissues to altered carbohydrate‐fat ratio in diet: An isoenergetic study in young rats. Genes %26 Nutrition, 12(1), 10. https://doi.org/10.1186/s12263-017-0558-2
Tang,, W. W., Dietmann,, S., Irie,, N., Leitch,, H. G., Floros,, V. I., Bradshaw,, C. R., … Surani,, M. A. (2015). A unique gene regulatory network resets the human germline epigenome for development. Cell, 161(6), 1453–1467. https://doi.org/10.1016/j.cell.2015.04.053
Tang,, W. W., Kobayashi,, T., Irie,, N., Dietmann,, S., & Surani,, M. A. (2016). Specification and epigenetic programming of the human germ line. Nature Reviews Genetics, 17(10), 585–600. https://doi.org/10.1038/nrg.2016.88
Tang,, Y., Wang,, J., Lian,, Y., Fan,, C., Zhang,, P., Wu,, Y., … Zeng,, Z. (2017). Linking long non‐coding RNAs and SWI/SNF complexes to chromatin remodeling in cancer. Molecular Cancer, 16, 42. https://doi.org/10.1186/s12943-017-0612-0
Tsukiyama,, T., Palmer,, J., Landel,, C. C., Shiloach,, J., & Wu,, C. (1999). Characterization of the imitation switch subfamily of ATP‐dependent chromatin‐remodeling factors in Saccharomyces cerevisiae. Genes %26 Development, 13(6), 686–697.
Tuorto,, F., Herbst,, F., Alerasool,, N., Bender,, S., Popp,, O., Federico,, G., … Lyko,, F. (2015). The tRNA methyltransferase Dnmt2 is required for accurate polypeptide synthesis during haematopoiesis. The EMBO Journal, 34(18), 2350–2362. https://doi.org/10.15252/embj.201591382
Tuorto,, F., Liebers,, R., Musch,, T., Schaefer,, M., Hofmann,, S., Kellner,, S., … Lyko,, F. (2012). RNA cytosine methylation by Dnmt2 and NSun2 promotes tRNA stability and protein synthesis. Nature Structural %26 Molecular Biology, 19(9), 900–905.
van der Heijden,, R. A., Sheedfar,, F., Morrison,, M. C., Hommelberg,, P. P., Kor,, D., Kloosterhuis,, N. J., … Heeringa,, P. (2015). High‐fat diet induced obesity primes inflammation in adipose tissue prior to liver in C57BL/6j mice. Aging (Albany NY), 7(4), 256–268. https://doi.org/10.18632/aging.100738
van der Wijst,, Monique,, G. P., Venkiteswaran,, M., Chen,, H., Xu,, G.‐L., Plösch,, T., & Rots,, M. G. (2015). Local chromatin microenvironment determines DNMT activity: From DNA methyltransferase to DNA demethylase or DNA dehydroxymethylase. Epigenetics, 10(8), 671–676. https://doi.org/10.1080/15592294.2015.1062204
Waddington,, C. H. (1942). Canalization of development and genetic assimilation of acquired characters. Nature, 150, 563–565.
Wahl,, S., Drong,, A., Lehne,, B., Loh,, M., Scott,, W. R., Kunze,, S., … Chambers,, J. C. (2017). Epigenome‐wide association study of body mass index, and the adverse outcomes of adiposity. Nature, 541(7635), 81–86. https://doi.org/10.1038/nature20784
Wang,, T., Tsui,, B., Kreisberg,, J. F., Robertson,, N. A., Gross,, A. M., Yu,, M. K., … Ideker,, T. (2017). Epigenetic aging signatures in mice livers are slowed by dwarfism, calorie restriction and rapamycin treatment. Genome Biology, 18, 57. https://doi.org/10.1186/s13059-017-1186-2
Waterland,, R. A., & Jirtle,, R. L. (2003). Transposable elements: Targets for early nutritional effects on epigenetic gene regulation. Molecular and Cellular Biology, 23(15), 5293–5300. https://doi.org/10.1128/MCB.23.15.5293-5300.2003
Weber,, C. M., & Henikoff,, S. (2014). Histone variants: Dynamic punctuation in transcription. Genes %26 Development, 28(7), 672–682. https://doi.org/10.1101/gad.238873.114
Weindruch,, R., Walford,, R. L., Fligiel,, S., & Guthrie,, D. (1986). The retardation of aging in mice by dietary restriction: Longevity, cancer, immunity and lifetime energy intake. Journal of Nutrition, 116(4), 641–654.
Whitelaw,, N. C., Chong,, S., Morgan,, D. K., Nestor,, C., Bruxner,, T. J., Ashe,, A., … Whitelaw,, E. (2010). Reduced levels of two modifiers of epigenetic gene silencing, Dnmt3a and Trim28, cause increased phenotypic noise. Genome Biology, 11, R111. https://doi.org/10.1186/gb-2010-11-11-r111
Winzell,, M. S., & Ahren,, B. (2004). The high‐fat diet‐fed mouse: A model for studying mechanisms and treatment of impaired glucose tolerance and type 2 diabetes. Diabetes, 53(Suppl. 3), S215–S219.
Writing Team for the Diabetes, Control, Complications Trial/Epidemiology of Diabetes, Interventions, %26 Complications Research Group (2003). Sustained effect of intensive treatment of type 1 diabetes mellitus on development and progression of diabetic nephropathy: The epidemiology of diabetes interventions and complications (EDIC) study. JAMA, 290(16), 2159–2167. https://doi.org/10.1001/jama.290.16.2159
Wu,, T. P., Wang,, T., Seetin,, M. G., Lai,, Y., Zhu,, S., Lin,, K., … Xiao,, A. Z. (2016). DNA methylation on N6‐adenine in mammalian embryonic stem cells. Nature, 532(7599), 329–333. https://doi.org/10.1038/nature17640
Zhao,, Y., Tan,, Y. S., Aupperlee,, M. D., Langohr,, I. M., Kirk,, E. L., Troester,, M. A., … Haslam,, S. Z. (2013). Pubertal high fat diet: Effects on mammary cancer development. Breast Cancer Research, 15(5), R100. https://doi.org/10.1186/bcr3561

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