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Cited by 249Epigenetics and DNA MethylationPancreatic function and diabetesDiabetes and associated disorders

Sex differences in the genome-wide DNA methylation pattern and impact on gene expression, microRNA levels and insulin secretion in human pancreatic islets

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Hall, Elin, Volkov, Petr, Dayeh, Tasnim, Esguerra, Jonathan Lou S, Salö, Sofia, Eliasson, Lena, Rönn, Tina, Bacos, Karl +1 more·2014·Genome Biology
DOI 10.1186/s13059-014-0522-zPMC PMC4256841
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Abstract

Background: Epigenetic factors regulate tissue-specific expression and X-chromosome inactivation. Previous studies have identified epigenetic differences between sexes in some human tissues. However, it is unclear whether epigenetic modifications contribute to sex-specific differences in insulin secretion and metabolism. Here, we investigate the impact of sex on the genome-wide DNA methylation pattern in human pancreatic islets from 53 males and 34 females, and relate the methylome to changes in expression and insulin secretion. Results: Glucose-stimulated insulin secretion is higher in female versus male islets. Genome-wide DNA methylation data in human islets clusters based on sex. While the chromosome-wide DNA methylation level on the X-chromosome is higher in female versus male islets, the autosomes do not display a global methylation difference between sexes. Methylation of 8,140 individual X-chromosome sites and 470 autosomal sites shows sex-specific differences in human islets. These include sites in/near AR , DUSP9 , HNF4A , BCL11A and CDKN2B . 61 X-chromosome genes and 18 autosomal genes display sex-specific differences in both DNA methylation and expression. These include NKAP , SPESP1 and APLN , which exhibited lower expression in females. Functional analyses demonstrate that methylation of NKAP and SPESP1 promoters in vitro suppresses their transcriptional activity. Silencing of Nkap or Apln in clonal beta-cells results in increased insulin secretion. Differential methylation between sexes is associated with altered levels of microRNAs miR-660 and miR-532 and related target genes. Conclusions: Chromosome-wide and gene-specific sex differences in DNA methylation associate with altered expression and insulin secretion in human islets. Our data demonstrate that epigenetics contribute to sex-specific metabolic phenotypes.

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  1. [1]Jirtle RL Skinner MK Environmental epigenomics and disease susceptibility Nat Rev Genet 2007 8 253 262 10.1038/nrg2045 17363974 PMC5940010 · DOI · Paper page
  2. [2]Lister R Pelizzola M Kida YS Hawkins RD Nery JR Hon G Antosiewicz-Bourget J O'Malley R Castanon R Klugman S Downes M Yu R Stewart R Ren B Thomson JA Evans RM Ecker JR Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells Nature 2011 471 68 73 10.1038/nature09798 21289626 PMC3100360 · DOI
  3. [3]Sarter B Long TI Tsong WH Koh WP Yu MC Laird PW Sex differential in methylation patterns of selected genes in Singapore Chinese Hum Genet 2005 117 402 403 10.1007/s00439-005-1317-9 15928902 · DOI
  4. [4]Eckhardt F Lewin J Cortese R Rakyan VK Attwood J Burger M Burton J Cox TV Davies R Down TA Haefliger C Horton R Howe K Jackson DK Kunde J Koenig C Liddle J Niblett D Otto T Pettett R Seemann S Thompson C West T Rogers J Olek A Berlin K Beck S DNA methylation profiling of human chromosomes 6, 20 and 22 Nat Genet 2006 38 1378 1385 10.1038/ng1909 17072317 PMC3082778 · DOI
  5. [5]El-Maarri O Becker T Junen J Manzoor SS Diaz-Lacava A Schwaab R Wienker T Oldenburg J Gender specific differences in levels of DNA methylation at selected loci from human total blood: a tendency toward higher methylation levels in males Hum Genet 2007 122 505 514 10.1007/s00439-007-0430-3 17851693 · DOI
  6. [6]Boks MP Derks EM Weisenberger DJ Strengman E Janson E Sommer IE Kahn RS Ophoff RA The relationship of DNA methylation with age, gender and genotype in twins and healthy controls PLoS One 2009 4 e6767 10.1371/journal.pone.0006767 19774229 PMC2747671 · DOI
  7. [7]Cotton AM Lam L Affleck JG Wilson IM Penaherrera MS McFadden DE Kobor MS Lam WL Robinson WP Brown CJ Chromosome-wide DNA methylation analysis predicts human tissue-specific X inactivation Hum Genet 2011 130 187 201 10.1007/s00439-011-1007-8 21597963 PMC3132437 · DOI
  8. [8]Hellman A Chess A Gene body-specific methylation on the active X chromosome Science 2007 315 1141 1143 10.1126/science.1136352 17322062 · DOI
  9. [9]Liu J Morgan M Hutchison K Calhoun VD A study of the influence of sex on genome wide methylation PLoS One 2010 5 e10028 10.1371/journal.pone.0010028 20386599 PMC2850313 · DOI
  10. [10]Brenet F Moh M Funk P Feierstein E Viale AJ Socci ND Scandura JM DNA methylation of the first exon is tightly linked to transcriptional silencing PLoS One 2011 6 e14524 10.1371/journal.pone.0014524 21267076 PMC3022582 · DOI
  11. [11]Aran D Toperoff G Rosenberg M Hellman A Replication timing-related and gene body-specific methylation of active human genes Hum Mol Genet 2011 20 670 680 10.1093/hmg/ddq513 21112978 · DOI · Paper page
  12. [12]Irizarry RA Ladd-Acosta C Wen B Wu Z Montano C Onyango P Cui H Gabo K Rongione M Webster M Ji H Potash JB Sabunciyan S Feinberg AP The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores Nat Genet 2009 41 178 186 10.1038/ng.298 19151715 PMC2729128 · DOI · Paper page
  13. [13]Ball MP Li JB Gao Y Lee JH LeProust EM Park IH Xie B Daley GQ Church GM Targeted and genome-scale strategies reveal gene-body methylation signatures in human cells Nat Biotechnol 2009 27 361 368 10.1038/nbt.1533 19329998 PMC3566772 · DOI
  14. [14]Rauch TA Wu X Zhong X Riggs AD Pfeifer GP A human B cell methylome at 100-base pair resolution Proc Natl Acad Sci U S A 2009 106 671 678 10.1073/pnas.0812399106 19139413 PMC2621253 · DOI
  15. [15]Lister R Pelizzola M Dowen RH Hawkins RD Hon G Tonti-Filippini J Nery JR Lee L Ye Z Ngo QM Edsall L Antosiewicz-Bourget J Stewart R Ruotti V Millar AH Thomson JA Ren B Ecker JR Human DNA methylomes at base resolution show widespread epigenomic differences Nature 2009 462 315 322 10.1038/nature08514 19829295 PMC2857523 · DOI · Paper page
  16. [16]Ronn T Volkov P Davegardh C Dayeh T Hall E Olsson AH Nilsson E Tornberg A Dekker Nitert M Eriksson KF Jones HA Groop L Ling C A six months exercise intervention influences the genome-wide DNA methylation pattern in human adipose tissue PLoS Genet 2013 9 e1003572 10.1371/journal.pgen.1003572 23825961 PMC3694844 · DOI
  17. [18]Basu R Dalla Man C Campioni M Basu A Klee G Toffolo G Cobelli C Rizza RA Effects of age and sex on postprandial glucose metabolism: differences in glucose turnover, insulin secretion, insulin action, and hepatic insulin extraction Diabetes 2006 55 2001 2014 10.2337/db05-1692 16804069 · DOI · Paper page
  18. [19]Kautzky-Willer A Brazzale AR Moro E Vrbikova J Bendlova B Sbrignadello S Tura A Pacini G Influence of increasing BMI on insulin sensitivity and secretion in normotolerant men and women of a wide age span Obesity (Silver Spring) 2012 20 1966 1973 10.1038/oby.2011.384 22282046 · DOI
  19. [20]Magkos F Wang X Mittendorfer B Metabolic actions of insulin in men and women Nutrition 2010 26 686 693 10.1016/j.nut.2009.10.013 20392600 PMC2893237 · DOI · Paper page
  20. [21]Stahle MU Brandhorst D Korsgren O Knutson F Pathogen inactivation of human serum facilitates its clinical use for islet cell culture and subsequent transplantation Cell Transplant 2011 20 775 781 10.3727/096368910X539056 21054939 · DOI
  21. [23]Chen YA Lemire M Choufani S Butcher DT Grafodatskaya D Zanke BW Gallinger S Hudson TJ Weksberg R Discovery of cross-reactive probes and polymorphic CpGs in the Illumina Infinium HumanMethylation450 microarray Epigenetics 2013 8 203 209 10.4161/epi.23470 23314698 PMC3592906 · DOI
  22. [24]Wang J Duncan D Shi Z Zhang B WEB-based GEne SeT AnaLysis Toolkit (WebGestalt): update 2013 Nucleic Acids Res 2013 41 W77 W83 10.1093/nar/gkt439 23703215 PMC3692109 · DOI
  23. [25]Zhang B Kirov S Snoddy J WebGestalt: an integrated system for exploring gene sets in various biological contexts Nucleic Acids Res 2005 33 W741 W748 10.1093/nar/gki475 15980575 PMC1160236 · DOI
  24. [26]Randall JC Winkler TW Kutalik Z Berndt SI Jackson AU Monda KL Kilpelainen TO Esko T Magi R Li S Workalemahu T Feitosa MF Croteau-Chonka DC Day FR Fall T Ferreira T Gustafsson S Locke AE Mathieson I Scherag A Vedantam S Wood AR Liang L Steinthorsdottir V Thorleifsson G Dermitzakis ET Dimas AS Karpe F Min JL Nicholson G Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits PLoS Genet 2013 9 e1003500 10.1371/journal.pgen.1003500 23754948 PMC3674993 · DOI
  25. [27]Lindgren CM Heid IM Randall JC Lamina C Steinthorsdottir V Qi L Speliotes EK Thorleifsson G Willer CJ Herrera BM Jackson AU Lim N Scheet P Soranzo N Amin N Aulchenko YS Chambers JC Drong A Luan J Lyon HN Rivadeneira F Sanna S Timpson NJ Zillikens MC Zhao JH Almgren P Bandinelli S Bennett AJ Bergman RN Bonnycastle LL Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution PLoS Genet 2009 5 e1000508 10.1371/journal.pgen.1000508 19557161 PMC2695778 · DOI
  26. [29]Carrel L Willard HF X-inactivation profile reveals extensive variability in X-linked gene expression in females Nature 2005 434 400 404 10.1038/nature03479 15772666 · DOI · Paper page
  27. [30]Ling C Groop L Epigenetics: a molecular link between environmental factors and type 2 diabetes Diabetes 2009 58 2718 2725 10.2337/db09-1003 19940235 PMC2780862 · DOI · Paper page
  28. [31]Jones PA Functions of DNA methylation: islands, start sites, gene bodies and beyond Nat Rev Genet 2012 13 484 492 10.1038/nrg3230 22641018 · DOI · Paper page
  29. [32]Chen D Li Z Yang Q Zhang J Zhai Z Shu HB Identification of a nuclear protein that promotes NF-kappaB activation Biochem Biophys Res Commun 2003 310 720 724 10.1016/j.bbrc.2003.09.074 14550261 · DOI
  30. [33]Ringstrom C Nitert MD Bennet H Fex M Valet P Rehfeld JF Friis-Hansen L Wierup N Apelin is a novel islet peptide Regul Pept 2010 162 44 51 10.1016/j.regpep.2010.03.005 20346374 · DOI
  31. [34]Wolkowicz MJ Digilio L Klotz K Shetty J Flickinger CJ Herr JC Equatorial segment protein (ESP) is a human alloantigen involved in sperm-egg binding and fusion J Androl 2008 29 272 282 10.2164/jandrol.106.000604 17978344 PMC2898563 · DOI
  32. [35]Niu MJ Yang JK Lin SS Ji XJ Guo LM Loss of angiotensin-converting enzyme 2 leads to impaired glucose homeostasis in mice Endocrine 2008 34 56 61 10.1007/s12020-008-9110-x 18956256 · DOI
  33. [36]Hinoi E Gao N Jung DY Yadav V Yoshizawa T Kajimura D Myers MG Jr Chua SC Jr Wang Q Kim JK Kaestner KH Karsenty G An Osteoblast-dependent mechanism contributes to the leptin regulation of insulin secretion Ann N Y Acad Sci 2009 1173 E20 E30 10.1111/j.1749-6632.2009.05061.x 19751411 · DOI
  34. [37]Simonis-Bik AM Nijpels G van Haeften TW Houwing-Duistermaat JJ Boomsma DI Reiling E van Hove EC Diamant M Kramer MH Heine RJ Maassen JA Slagboom PE Willemsen G Dekker JM Eekhoff EM de Geus EJ t Hart LM Gene variants in the novel type 2 diabetes loci CDC123/CAMK1D, THADA, ADAMTS9, BCL11A, and MTNR1B affect different aspects of pancreatic beta-cell function Diabetes 2010 59 293 301 10.2337/db09-1048 19833888 PMC2797936 · DOI
  35. [38]Hribal ML Presta I Procopio T Marini MA Stancakova A Kuusisto J Andreozzi F Hammarstedt A Jansson PA Grarup N Hansen T Walker M Stefan N Fritsche A Haring HU Pedersen O Smith U Laakso M Sesti G Glucose tolerance, insulin sensitivity and insulin release in European non-diabetic carriers of a polymorphism upstream of CDKN2A and CDKN2B Diabetologia 2011 54 795 802 10.1007/s00125-010-2038-8 21234743 · DOI
  36. [39]Foti D Chiefari E Fedele M Iuliano R Brunetti L Paonessa F Manfioletti G Barbetti F Brunetti A Croce CM Fusco A Lack of the architectural factor HMGA1 causes insulin resistance and diabetes in humans and mice Nat Med 2005 11 765 773 10.1038/nm1254 15924147 · DOI
  37. [40]Gupte M Thatcher SE Boustany-Kari CM Shoemaker R Yiannikouris F Zhang X Karounos M Cassis LA Angiotensin converting enzyme 2 contributes to sex differences in the development of obesity hypertension in C57BL/6 mice Arterioscler Thromb Vasc Biol 2012 32 1392 1399 10.1161/ATVBAHA.112.248559 22460555 PMC3355213 · DOI
  38. [41]Stanley JA Aruldhas MM Yuvaraju PB Banu SK Anbalagan J Neelamohan R Annapoorna K Jayaraman G Is gender difference in postnatal thyroid growth associated with specific expression patterns of androgen and estrogen receptors? Steroids 2010 75 1058 1066 10.1016/j.steroids.2010.06.009 20670640 · DOI
  39. [42]Castagne R Zeller T Rotival M Szymczak S Truong V Schillert A Tregouet DA Munzel T Ziegler A Cambien F Blankenberg S Tiret L Influence of sex and genetic variability on expression of X-linked genes in human monocytes Genomics 2011 98 320 326 10.1016/j.ygeno.2011.06.009 21763416 · DOI
  40. [43]Qu M Tang F Wang L Yan H Han Y Yan J Yue W Zhang D Associations of ATF4 gene polymorphisms with schizophrenia in male patients Am J Med Genet B Neuropsychiatr Genet 2008 147B 732 736 10.1002/ajmg.b.30675 18163433 · DOI
  41. [44]Orozco G Ioannidis JP Morris A Zeggini E Sex-specific differences in effect size estimates at established complex trait loci Int J Epidemiol 2012 41 1376 1382 10.1093/ije/dys104 22825589 PMC3465768 · DOI
  42. [45]Tabernero MD Espinosa AB Maillo A Rebelo O Vera JF Sayagues JM Merino M Diaz P Sousa P Orfao A Patient gender is associated with distinct patterns of chromosomal abnormalities and sex chromosome linked gene-expression profiles in meningiomas Oncologist 2007 12 1225 1236 10.1634/theoncologist.12-10-1225 17962616 · DOI
  43. [46]Reinius B Johansson MM Radomska KJ Morrow EH Pandey GK Kanduri C Sandberg R Williams RW Jazin E Abundance of female-biased and paucity of male-biased somatically expressed genes on the mouse X-chromosome BMC Genomics 2012 13 607 10.1186/1471-2164-13-607 23140559 PMC3534601 · DOI
  44. [47]Mozhui K Lu L Armstrong WE Williams RW Sex-specific modulation of gene expression networks in murine hypothalamus Front Neurosci 2012 6 63 10.3389/fnins.2012.00063 22593731 PMC3350311 · DOI
  45. [48]Taniwaki M Takano A Ishikawa N Yasui W Inai K Nishimura H Tsuchiya E Kohno N Nakamura Y Daigo Y Activation of KIF4A as a prognostic biomarker and therapeutic target for lung cancer Clin Cancer Res 2007 13 6624 6631 10.1158/1078-0432.CCR-07-1328 18006763 · DOI
  46. [49]Nino-Soto MI Nuber UA Basrur PK Ropers HH King WA Differences in the pattern of X-linked gene expression between fetal bovine muscle and fibroblast cultures derived from the same muscle biopsies Cytogenet Genome Res 2005 111 57 64 10.1159/000085671 16093722 · DOI
  47. [50]Muller CR Migl B Traupe H Ropers HH X-linked steroid sulfatase: evidence for different gene-dosage in males and females Hum Genet 1980 54 197 199 10.1007/BF00278971 6930360 · DOI
  48. [51]Yazarloo F Shirkoohi R Mobasheri MB Emami A Modarressi MH Expression analysis of four testis-specific genes AURKC, OIP5, PIWIL2 and TAF7L in acute myeloid leukemia: a gender-dependent expression pattern Med Oncol 2013 30 368 10.1007/s12032-012-0368-8 23292864 · DOI
  49. [52]Kameswaran V Bramswig NC McKenna LB Penn M Schug J Hand NJ Chen Y Choi I Vourekas A Won KJ Liu C Vivek K Naji A Friedman JR Kaestner KH Epigenetic Regulation of the DLK1-MEG3 MicroRNA Cluster in Human Type 2 Diabetic Islets Cell Metab 2014 19 135 145 10.1016/j.cmet.2013.11.016 24374217 PMC3932527 · DOI
  50. [55]Lee DK Cheng R Nguyen T Fan T Kariyawasam AP Liu Y Osmond DH George SR O'Dowd BF Characterization of apelin, the ligand for the APJ receptor J Neurochem 2000 74 34 41 10.1046/j.1471-4159.2000.0740034.x 10617103 · DOI
  51. [56]Guo L Li Q Wang W Yu P Pan H Li P Sun Y Zhang J Apelin inhibits insulin secretion in pancreatic beta-cells by activation of PI3-kinase-phosphodiesterase 3B Endocr Res 2009 34 142 154 10.3109/07435800903287079 19878074 · DOI
  52. [57]Pahl HL Activators and target genes of Rel/NF-kappaB transcription factors Oncogene 1999 18 6853 6866 10.1038/sj.onc.1203239 10602461 · DOI · Paper page
  53. [58]Eizirik DL Sandler S Welsh N Cetkovic-Cvrlje M Nieman A Geller DA Pipeleers DG Bendtzen K Hellerstrom C Cytokines suppress human islet function irrespective of their effects on nitric oxide generation J Clin Invest 1994 93 1968 1974 10.1172/JCI117188 7514190 PMC294304 · DOI
  54. [59]Bendtzen K Mandrup-Poulsen T Nerup J Nielsen JH Dinarello CA Svenson M Cytotoxicity of human pI 7 interleukin-1 for pancreatic islets of Langerhans Science 1986 232 1545 1547 10.1126/science.3086977 3086977 · DOI
  55. [60]Mahdi T Hanzelmann S Salehi A Muhammed SJ Reinbothe TM Tang Y Axelsson AS Zhou Y Jing X Almgren P Krus U Taneera J Blom AM Lyssenko V Esguerra JL Hansson O Eliasson L Derry J Zhang E Wollheim CB Groop L Renstrom E Rosengren AH Secreted frizzled-related protein 4 reduces insulin secretion and is overexpressed in type 2 diabetes Cell Metab 2012 16 625 633 10.1016/j.cmet.2012.10.009 23140642 · DOI
  56. [62]Yu Y Wang J Khaled W Burke S Li P Chen X Yang W Jenkins NA Copeland NG Zhang S Liu P Bcl11a is essential for lymphoid development and negatively regulates p53 J Exp Med 2012 209 2467 2483 10.1084/jem.20121846 23230003 PMC3526365 · DOI
  57. [63]Gao Y Wu H He D Hu X Li Y Downregulation of BCL11A by siRNA induces apoptosis in B lymphoma cell lines Biomed Rep 2013 1 47 52 24648892 PMC3956826
  58. [64]He D Wu H Ding L Li Y Combination of BCL11A siRNA with vincristine increases the apoptosis of SUDHL6 cells Eur J Med Res 2014 19 34 10.1186/2047-783X-19-34 24961604 PMC4086990 · DOI
  59. [65]Wu H Li Y Gene expression profile analysis of SUDHL6 cells with siRNA-mediated BCL11 A downregulation Cell Biol Int 2014 38 1205 1214 10.1002/cbin.10272 25044937 · DOI
  60. [66]Cauchi S Ezzidi I El Achhab Y Mtiraoui N Chaieb L Salah D Nejjari C Labrune Y Yengo L Beury D Vaxillaire M Mahjoub T Chikri M Froguel P European genetic variants associated with type 2 diabetes in North African Arabs Diabetes Metab 2012 38 316 323 10.1016/j.diabet.2012.02.003 22463974 · DOI
  61. [67]Jonsson A Ladenvall C Ahluwalia TS Kravic J Krus U Taneera J Isomaa B Tuomi T Renstrom E Groop L Lyssenko V Effects of common genetic variants associated with type 2 diabetes and glycemic traits on alpha- and beta-cell function and insulin action in humans Diabetes 2013 62 2978 2983 10.2337/db12-1627 23557703 PMC3717852 · DOI
  62. [68]Langberg KA Ma L Sharma NK Hanis CL Elbein SC Hasstedt SJ Das SK Single nucleotide polymorphisms in JAZF1 and BCL11A gene are nominally associated with type 2 diabetes in African-American families from the GENNID study J Hum Genet 2012 57 57 61 10.1038/jhg.2011.133 22113416 PMC3266455 · DOI
  63. [69]Tang L Wang L Ye H Xu X Hong Q Wang H Xu L Bu S Zhang L Cheng J Liu P Ye M Mai Y Duan S BCL11A gene DNA methylation contributes to the risk of type 2 diabetes in males Exp Ther Med 2014 8 459 463 25009601 PMC4079426
  64. [70]Bindom SM Hans CP Xia H Boulares AH Lazartigues E Angiotensin I-converting enzyme type 2 (ACE2) gene therapy improves glycemic control in diabetic mice Diabetes 2010 59 2540 2548 10.2337/db09-0782 20660625 PMC3279528 · DOI
  65. [71]Chhabra KH Xia H Pedersen KB Speth RC Lazartigues E Pancreatic angiotensin-converting enzyme 2 improves glycemia in angiotensin II-infused mice Am J Physiol Endocrinol Metab 2013 304 E874 E884 10.1152/ajpendo.00490.2012 23462816 PMC3625779 · DOI
  66. [72]Kode A Mosialou I Silva BC Joshi S Ferron M Rached MT Kousteni S FoxO1 protein cooperates with ATF4 protein in osteoblasts to control glucose homeostasis J Biol Chem 2012 287 8757 8768 10.1074/jbc.M111.282897 22298775 PMC3308768 · DOI
  67. [73]Yoshizawa T Hinoi E Jung DY Kajimura D Ferron M Seo J Graff JM Kim JK Karsenty G The transcription factor ATF4 regulates glucose metabolism in mice through its expression in osteoblasts J Clin Invest 2009 119 2807 2817 10.1172/JCI39366 19726872 PMC2735903 · DOI
  68. [74]Liew CW Bochenski J Kawamori D Hu J Leech CA Wanic K Malecki M Warram JH Qi L Krolewski AS Kulkarni RN The pseudokinase tribbles homolog 3 interacts with ATF4 to negatively regulate insulin exocytosis in human and mouse beta cells J Clin Invest 2010 120 2876 2888 10.1172/JCI36849 20592469 PMC2912176 · DOI
  69. [75]Lin HM Lee JH Yadav H Kamaraju AK Liu E Zhigang D Vieira A Kim SJ Collins H Matschinsky F Harlan DM Roberts AB Rane SG Transforming growth factor-beta/Smad3 signaling regulates insulin gene transcription and pancreatic islet beta-cell function J Biol Chem 2009 284 12246 12257 10.1074/jbc.M805379200 19265200 PMC2673293 · DOI
  70. [76]Morgan CP Bale TL Sex differences in microRNA regulation of gene expression: no smoke, just miRs Biol Sex Differ 2012 3 22 10.1186/2042-6410-3-22 23009289 PMC3507674 · DOI
  71. [77]Wang H Maechler P Antinozzi PA Hagenfeldt KA Wollheim CB Hepatocyte nuclear factor 4alpha regulates the expression of pancreatic beta -cell genes implicated in glucose metabolism and nutrient-induced insulin secretion J Biol Chem 2000 275 35953 35959 10.1074/jbc.M006612200 10967120 · DOI
  72. [78]Chen YA Choufani S Ferreira JC Grafodatskaya D Butcher DT Weksberg R Sequence overlap between autosomal and sex-linked probes on the Illumina HumanMethylation27 microarray Genomics 2011 97 214 222 10.1016/j.ygeno.2010.12.004 21211562 · DOI · Paper page
  73. [79]Jeppsson JO Jerntorp P Sundkvist G Englund H Nylund V Measurement of hemoglobin A1c by a new liquid-chromatographic assay: methodology, clinical utility, and relation to glucose tolerance evaluated Clin Chem 1986 32 1867 1872 3757206
  74. [80]Olsson AH Yang BT Hall E Taneera J Salehi A Nitert MD Ling C Decreased expression of genes involved in oxidative phosphorylation in human pancreatic islets from patients with type 2 diabetes Eur J Endocrinol 2011 165 589 595 10.1530/EJE-11-0282 21775499 PMC3178933 · DOI
  75. [83]Vikman J Jimenez-Feltstrom J Nyman P Thelin J Eliasson L Insulin secretion is highly sensitive to desorption of plasma membrane cholesterol FASEB J 2009 23 58 67 10.1096/fj.08-105734 18806218 · DOI · Paper page
  76. [84]Teschendorff AE Menon U Gentry-Maharaj A Ramus SJ Gayther SA Apostolidou S Jones A Lechner M Beck S Jacobs IJ Widschwendter M An epigenetic signature in peripheral blood predicts active ovarian cancer PLoS One 2009 4 e8274 10.1371/journal.pone.0008274 20019873 PMC2793425 · DOI
  77. [85]Du P Zhang X Huang CC Jafari N Kibbe WA Hou L Lin SM Comparison of Beta-value and M-value methods for quantifying methylation levels by microarray analysis BMC Bioinformatics 2010 11 587 10.1186/1471-2105-11-587 21118553 PMC3012676 · DOI · Paper page
  78. [86]Du P Kibbe WA Lin SM lumi: a pipeline for processing Illumina microarray Bioinformatics 2008 24 1547 1548 10.1093/bioinformatics/btn224 18467348 · DOI
  79. [89]Irizarry RA Bolstad BM Collin F Cope LM Hobbs B Speed TP Summaries of Affymetrix GeneChip probe level data Nucleic Acids Res 2003 31 e15 10.1093/nar/gng015 12582260 PMC150247 · DOI
  80. [90]Rainer J Sanchez-Cabo F Stocker G Sturn A Trajanoski Z CARMAweb: comprehensive R- and bioconductor-based web service for microarray data analysis Nucleic Acids Res 2006 34 W498 W503 10.1093/nar/gkl038 16845058 PMC1538903 · DOI
  81. [92]Klug M Rehli M Functional analysis of promoter CpG methylation using a CpG-free luciferase reporter vector Epigenetics 2006 1 127 130 10.4161/epi.1.3.3327 17965610 · DOI
  82. [93]Hohmeier HE Mulder H Chen G Henkel-Rieger R Prentki M Newgard CB Isolation of INS-1-derived cell lines with robust ATP-sensitive K+ channel-dependent and -independent glucose-stimulated insulin secretion Diabetes 2000 49 424 430 10.2337/diabetes.49.3.424 10868964 · DOI

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Authors
Hall, E., Volkov, P., Dayeh, T., Esguerra, J. L. S., Salö, S., Eliasson, L., Rönn, T., Bacos, K., & Ling, C.
Affiliations
Lund University (SE)
Corresponding author
Ling, Charlotte
ORCID
Venue
Genome Biology
Publisher
Springer Science and Business Media LLC
Published
2014-12-03
Volume
15
Issue
12
Pages
522-522
ISSN
  • 1465-6906 (ISSN-L)
  • 1474-760X
DOI
10.1186/s13059-014-0522-z
PMC
PMC4256841
OpenAlex
W2164441586
Cited by
249
References
9
Citations by year
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FWCI
5.61
Type
journal article
Language
en
Open access
Licence
Locations
  • Genome biology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Lund University Publications (Lund University) (submittedVersion, other-oa)
Funders
  • Eli Lilly and Company
  • European Foundation for the Study of Diabetes (B31 5631/2006)
  • Lunds Universitet
  • Knut och Alice Wallenbergs Stiftelse
  • Novo Nordisk
  • Vetenskapsrådet
  • Novo Nordisk Fonden (NNF11OC1014546)
  • Region Skåne
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
Keywords
sex differences, DNA methylation, pancreatic islets, insulin secretion, X chromosome methylation, X chromosome inactivation, gene expression, microRNA, NKAP, apelin, pancreatic beta cells, epigenetics
MeSH terms
Insulin Secretion, Aged, Female, Humans, Insulin, Islets of Langerhans, Male, Middle Aged, Molecular Sequence Data, Sex Characteristics, Gene Expression, Genome, Human, CpG Islands, DNA Methylation, MicroRNAs, Epigenesis, Genetic

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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