期刊论文详细信息
Clinical Epigenetics
Global differences in specific histone H3 methylation are associated with overweight and type 2 diabetes
Peter Strålfors1  Alexander V Vener1  Risul Amin1  Kim Lundqvist1  Simon Sjödin1  Åsa Jufvas1 
[1] Department of Clinical and Experimental Medicine, Linköping University, Linköping SE58185, Sweden
关键词: Type 2 diabetes;    Primary mature adipocytes;    Overweight;    Obesity;    Human;    Histone methylation;    Epigenetic;   
Others  :  790894
DOI  :  10.1186/1868-7083-5-15
 received in 2013-05-01, accepted in 2013-07-12,  发布年份 2013
PDF
【 摘 要 】

Background

Epidemiological evidence indicates yet unknown epigenetic mechanisms underlying a propensity for overweight and type 2 diabetes. We analyzed the extent of methylation at lysine 4 and lysine 9 of histone H3 in primary human adipocytes from 43 subjects using modification-specific antibodies.

Results

The level of lysine 9 dimethylation was stable, while adipocytes from type 2 diabetic and non-diabetic overweight subjects exhibited about 40% lower levels of lysine 4 dimethylation compared with cells from normal-weight subjects. In contrast, trimethylation at lysine 4 was 40% higher in adipocytes from overweight diabetic subjects compared with normal-weight and overweight non-diabetic subjects. There was no association between level of modification and age of subjects.

Conclusions

The findings define genome-wide molecular modifications of histones in adipocytes that are directly associated with overweight and diabetes, and thus suggest a molecular basis for existing epidemiological evidence of epigenetic inheritance.

【 授权许可】

   
2013 Jufvas et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20140705004803642.pdf 462KB PDF download
Figure 4. 36KB Image download
Figure 3. 46KB Image download
Figure 6. 37KB Image download
Figure 1. 31KB Image download
【 图 表 】

Figure 1.

Figure 6.

Figure 3.

Figure 4.

【 参考文献 】
  • [1]Zentner GE, Henikoff S: Regulation of nucleosome dynamics by histone modifications. Nat Struct Mol Biol 2013, 20:259-266.
  • [2]Phillips DMP: The presence of acetyl groups in histones. Biochem J 1961, 87:258-263.
  • [3]Pogo BG, Allfrey VG, Mirsky AE: RNA synthesis and histone acetylation during the course of gene activation in lymphocytes. Proc Natl Acad Sci USA 1966, 55:805-812.
  • [4]Orford K, Kharchenko P, Lai W, Dao MC, Worhunsky DJ, Ferro A, Janzen V, Park PJ, Scadden DT: Differential H3K4 methylation identifies developmentally poised hematopoietic genes. Devel Cell 2008, 14:798-809.
  • [5]Kouzarides T: Chromatin modifications and their function. Cell 2007, 128:693-705.
  • [6]Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, Wei G, Chepelev I, Zhao K: High-resolution profiling of histone methylations in the human genome. Cell 2007, 129:823-837.
  • [7]Wang Z, Schones DE, Zhao K: Characterization of human epigenomes. Curr Opin Genet Dev 2009, 19:127-134.
  • [8]Zhang Y, Reinberg D: Transcription regulation by histone methylation: interplay between different covalent modifications of the core histone tails. Gen Devel 2001, 15:2343-2360.
  • [9]Teperino R, Schoonjans K, Auwerx J: Histone methyl transferases and demethylases; can they link metabolism and transcription? Cell Metab 2010, 12:321-327.
  • [10]Doria A, Patti ME, Kahn CR: The emerging genetic architecture of type 2 diabetes. Cell Metab 2008, 8:186-200.
  • [11]Billings LK, Florez JC: The genetics of type 2 diabetes: what have we learned from GWAS? Ann New York Acad Sci 2010, 1212:59-77.
  • [12]Drong AW, Lindgren CM, McCarthy MI: The genetic and epigenetic basis of type 2 diabetes and obesity. Clin Pharmacol Ther 2012, 92:707-715.
  • [13]Sandholt CH, Hansen T, Pedersen O: Beyond the fourth wave of genome-wide obesity association studies. Nutr Diabetes 2012, 2:e37.
  • [14]Ravelli AC, van der Meulen JH, Michels RP, Osmond C, Barker DJ, Hales CN, Bleker OP: Glucose tolerance in adults after prenatal exposure to famine. Lancet 1998, 351:173-177.
  • [15]Ravelli AC, van Der Meulen JH, Osmond C, Barker DJ, Bleker OP: Obesity at the age of 50 y in men and women exposed to famine prenatally. Am J Clin Nutr 1999, 70:811-816.
  • [16]Heijmans BT, Tobi EW, Stein AD, Putter H, Blauw GJ, Susser ES, Slagboom PE, Lumey LH: Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci USA 2008, 105:17046-17049.
  • [17]Kaati G, Bygren LO, Edvinsson S: Cardiovascular and diabetes mortality determined by nutrition during parents’ and grandparents’ slow growth period. Eur J Hum Gen 2002, 10:682-688.
  • [18]Thurner S, Klimek P, Szell M, Duftschmid G, Endel G, Kautzky-Willer A, Kasper DC: Quantification of excess risk for diabetes for those born in times of hunger, in an entire population of a nation, across a century. Proc Natl Acad Sci USA 2013, 110:4703-4707.
  • [19]Jousse C, Parry L, Lambert-Langlais S, Maurin AC, Averous J, Bruhat A, Carraro V, Tost J, Letteron P, Chen P, Jockers R, Launay JM, Mallet J, Fafournoux P: Perinatal undernutrition affects the methylation and expression of the leptin gene in adults: implication for the understanding of metabolic syndrome. FASEB J 2011, 25:3271-3278.
  • [20]Raychaudhuri N, Raychaudhuri S, Thamotharan M, Devaskar SU: Histone code modifications repress glucose transporter 4 expression in the intrauterine growth-restricted offspring. J Biol Chem 2008, 283:13611-13626.
  • [21]Seki Y, Williams L, Vuguin PM, Charron MJ: Minireview. Epigenetic programming of diabetes and obesity: animal models. Endocrinology 2012, 153:1031-1038.
  • [22]Ng S-F, Lin RCY, Laybutt DR, Barres R, Owens JA, Morris MJ: Chronic high-fat diet in fathers programs β-cell dysfunction in female rat offspring. Nature 2010, 467:963-966.
  • [23]Carone BR, Fauquier L, Habib N, Shea JM, Hart CE, Li R, Bock C, Li C, Gu H, Zamore PD, Meissner A, Weng Z, Hofmann HA, Friedman N, Rando OJ: Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals. Cell 2010, 143:1084-1096.
  • [24]Feinberg AP, Irizarry RA, Fradin D, Aryee MJ, Murakami P, Aspelund T, Eiriksdottir G, Harris TB, Launer L, Gudnason V, Fallin MD: Personalized epigenomic signatures that are stable over time and covary with body mass index. Sci Transl Med 2010, 2:49ra-67ra.
  • [25]Han S, Brunet A: Histone methylation makes its mark on longevity. Trends Cell Biol 2012, 22:42-49.
  • [26]Dabelea D, Hanson RL, Lindsay RS, Pettitt DJ, Imperatore G, Gabir MM, Roumain J, Bennett PH, Knowler WC: Intrauterine exposure to diabetes conveys risks for type 2 diabetes and obesity: a study of discordant sibships. Diabetes 2000, 49:2208-2211.
  • [27]Oge A, Isganaitis E, Jimenez-Chillaron J, Reamer C, Faucette R, Barry K, Przybyla R, Patti ME: In utero undernutrition reduces diabetes incidence in non-obese diabetic mice. Diabetologia 2007, 50:1099-1108.
  • [28]Park JH, Stoffers DA, Nicholls RD, Simmons RA: Development of type 2 diabetes following intrauterine growth retardation in rats is associated with progressive epigenetic silencing of Pdx1. J Clin Invest 2008, 118:2316-2324.
  • [29]Brasacchio D, Okabe J, Tikellis C, Balcerczyk A, George P, Baker EK, Calkin AC, Brownlee M, Cooper ME, El-Osta A: Hyperglycemia induces a dynamic cooperativity of histone methylase and demethylase enzymes associated with gene-activating epigenetic marks that co-exist on the lysine tail. Diabetes 2009, 58:1229-1236.
  • [30]El-Osta A, Brasacchio D, Yao D, Pocai A, Jones PL, Roeder RG, Cooper ME, Brownlee M: Transient high glucose causes persistent epigenetic changes and altered gene expression during subsequent normoglycemia. J Exp Med 2008, 205:2409-2417.
  • [31]Barrès R, Yan J, Egan B: Treebak Jonas T, Rasmussen M, Fritz T, Caidahl K, Krook A, O’Gorman Donal J, Zierath Juleen R: Acute exercise remodels promoter methylation in human skeletal muscle. Cell Metab 2012, 15:405-411.
  • [32]Feinberg AP: Epigenetics at the epicenter of modern medicine. J Am Med Assoc 2008, 299:1345-1350.
  • [33]Fang R, Barbera AJ, Xu Y, Rutenberg M, Leonor T, Bi Q, Lan F, Mei P, Yuan GC, Lian C, Peng J, Cheng D, Sui G, Kaiser UB, Shi Y, Shi YG: Human LSD2/KDM1b/AOF1 regulates gene transcription by modulating intragenic H3K4me2 methylation. Mol Cell 2010, 39:222-233.
  • [34]Hino S, Sakamoto A, Nagaoka K, Anan K, Wang Y, Mimasu S, Umehara T, Yokoyama S, Kosai K, Nakao M: FAD-dependent lysine-specific demethylase-1 regulates cellular energy expenditure. Nat Commun 2012, 3:758.
  • [35]Shi Y, Lan F, Matson C, Mulligan P, Whetstine JR, Cole PA, Casero RA, Shi Y: Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 2004, 119:941-953.
  • [36]Lee MG, Wynder C, Schmidt DM, McCafferty DG, Shiekhattar R: Histone H3 lysine 4 demethylation is a target of nonselective antidepressive medications. Chem Biol 2006, 13:563-567.
  • [37]Shilatifard A: Molecular implementation and physiological roles for histone H3 lysine 4 (H3K4) methylation. Curr Opin Cell Biol 2008, 20:341-348.
  • [38]Lee J, Saha PK, Yang QH, Lee S, Park JY, Suh Y, Lee SK, Chan L, Roeder RG, Lee JW: Targeted inactivation of MLL3 histone H3-Lys-4 methyltransferase activity in the mouse reveals vital roles for MLL3 in adipogenesis. Proc Natl Acad Sci USA 2008, 105:19229-19234.
  • [39]Yang Q, Graham TE, Mody N, Preitner F, Peroni OD, Zabolotny JM, Kotani K, Quadro L, Kahn BB: Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature 2005, 436:356-362.
  • [40]Öst A, Danielsson A, Lidén M, Eriksson U, Nystrom FH, Strålfors P: Retinol-binding protein-4 attenuates insulin-induced phosphorylation of IRS1 and ERK1/2 in primary human adipocytes. FASEB J 2007, 21:3696-3704.
  • [41]Mikkelsen TS, Xu Z, Zhang X, Wang L, Gimble JM, Lander ES, Rosen ED: Comparative epigenomic analysis of murine and human adipogenesis. Cell 2010, 143:156-169.
  • [42]Wang L, Xu S, Lee J-E, Baldridge A, Grullon S, Peng W, Ge K: Histone H3K9 methyltransferase G9a represses PPARgamma expression and adipogenesis. EMBO J 2013, 32:45-59.
  • [43]Strålfors P, Honnor RC: Insulin-induced dephosphorylation of hormone-sensitive lipase. Correlation with lipolysis and cAMP-dependent protein kinase activity. Eur J Biochem 1989, 182:379-385.
  • [44]Danielsson A, Öst A, Lystedt E, Kjolhede P, Gustavsson J, Nystrom FH, Strålfors P: Insulin resistance in human adipocytes occurs downstream of IRS1 after surgical cell isolation but at the level of phosphorylation of IRS1 in type 2 diabetes. FEBS J 2005, 272:141-151.
  • [45]Honnor RC, Dhillon GS, Londos C: cAMP-dependent protein kinase and lipolysis in rat adipocytes. I. Cell preparation, manipulation, and predictability in behavior. J Biol Chem 1985, 260:15122-15129.
  • [46]Laemmli UK: Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970, 227:680-685.
  文献评价指标  
  下载次数:22次 浏览次数:6次