{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T20:27:03Z","timestamp":1788899223676,"version":"build-2803163510"},"reference-count":41,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2016,9,15]],"date-time":"2016-09-15T00:00:00Z","timestamp":1473897600000},"content-version":"vor","delay-in-days":258,"URL":"http:\/\/www.biologists.com\/user-licence-1-1"}],"funder":[{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"publisher","award":["NMRC\/TCR\/004-NUS\/2008"],"award-info":[{"award-number":["NMRC\/TCR\/004-NUS\/2008"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001348","name":"Agency for Science Technology and Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001348","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,1,1]]},"abstract":"<jats:p>The association between impaired fetal growth and postnatal development of obesity has been demonstrated before. By comparing adipocytes differentiated from Mesenchymal Stem Cells (MSCs) taken from the umbilical cord and derived from normal and growth restricted neonates, we identified the transcription factor SOX6 as a highly expressed gene only in growth restricted individuals. We found that SOX6 regulates the process of adipogenesis in vertebrate species by activating adipogenic regulators including PPAR\u03b3, C\/EBP\u03b1, and MEST. We further show that SOX6 interacts with \u03b2-catenin in adipocytes suggesting an inhibition of WNT\/\u03b2-catenin signaling thereby promoting adipogenesis. The upstream regulatory region of the MEST gene in MSCs from growth restricted subjects harbors hypo-methylated CpGs next to SOX6 binding motifs and we found that SOX6 binding is impaired by adjacent CpG methylation. In summary, we report that SOX6 is a novel regulator of adipogenesis synergizing with epigenetic mechanisms.<\/jats:p>","DOI":"10.1242\/dev.131573","type":"journal-article","created":{"date-parts":[[2016,2,19]],"date-time":"2016-02-19T04:20:34Z","timestamp":1455855634000},"source":"Crossref","is-referenced-by-count":34,"title":["The transcription factor SOX6 contributes to the developmental origins of obesity by promoting adipogenesis"],"prefix":"10.1242","author":[{"given":"Shi Chi","family":"Leow","sequence":"first","affiliation":[{"name":"Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremie","family":"Poschmann","sequence":"additional","affiliation":[{"name":"Genome Institute of Singapore, Agency for Science Technology and Research (A*STAR), Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peh Gek","family":"Too","sequence":"additional","affiliation":[{"name":"Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Yin","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roy","family":"Joseph","sequence":"additional","affiliation":[{"name":"Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"McFarlane","sequence":"additional","affiliation":[{"name":"Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaillay","family":"Dogra","sequence":"additional","affiliation":[{"name":"Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asim","family":"Shabbir","sequence":"additional","affiliation":[{"name":"Department of Surgery, National University Hospital, National University of Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip W.","family":"Ingham","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore"},{"name":"Institute of Molecular and Cell Biology, Agency for Science Technology and Research (A*STAR), Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyam","family":"Prabhakar","sequence":"additional","affiliation":[{"name":"Genome Institute of Singapore, Agency for Science Technology and Research (A*STAR), Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melvin K. S.","family":"Leow","sequence":"additional","affiliation":[{"name":"Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore"},{"name":"Department of Endocrinology, Tan Tock Seng Hospital, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yung Seng","family":"Lee","sequence":"additional","affiliation":[{"name":"Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore"},{"name":"Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai Lyn","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yap Seng","family":"Chong","sequence":"additional","affiliation":[{"name":"Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore"},{"name":"Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter D.","family":"Gluckman","sequence":"additional","affiliation":[{"name":"Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore"},{"name":"Liggins Institute, University of Auckland, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"St\u00fcnkel","sequence":"additional","affiliation":[{"name":"Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042608482726300_DEV131573C1","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1016\/j.neuron.2009.08.005","article-title":"The cell-intrinsic requirement of Sox6 for cortical interneuron development","volume":"63","author":"Batista-Brito","year":"2009","journal-title":"Neuron"},{"key":"2021042608482726300_DEV131573C2","doi-asserted-by":"publisher","first-page":"964236","DOI":"10.1155\/2014\/964236","article-title":"Overweight and obesity epidemic in developing countries: a problem with diet, physical activity, or socioeconomic status?","volume":"2014","author":"Bhurosy","year":"2014","journal-title":"Sci. World J."},{"key":"2021042608482726300_DEV131573C3","doi-asserted-by":"publisher","first-page":"e73950","DOI":"10.1371\/journal.pone.0073950","article-title":"Genetic effects on DNA methylation and its potential relevance for obesity in Mexican Americans","volume":"8","author":"Carless","year":"2013","journal-title":"PLoS ONE"},{"key":"2021042608482726300_DEV131573C4","doi-asserted-by":"publisher","first-page":"1406","DOI":"10.1097\/HJH.0b013e3283610fed","article-title":"Recruitment of specificity protein 1 by CpG hypomethylation upregulates Na+;-K+-2Cl\u2212 cotransporter 1 in hypertensive rats","volume":"31","author":"Cho","year":"2013","journal-title":"J. Hypertens."},{"key":"2021042608482726300_DEV131573C5","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1056\/NEJM199602013340503","article-title":"Serum immunoreactive-leptin concentrations in normal-weight and obese humans","volume":"334","author":"Considine","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"2021042608482726300_DEV131573C6","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1093\/ajcn\/86.4.1219","article-title":"The metabolic syndrome in adults prenatally exposed to the Dutch famine","volume":"86","author":"de Rooij","year":"2007","journal-title":"Am. J. Clin. Nutr."},{"key":"2021042608482726300_DEV131573C7","doi-asserted-by":"publisher","first-page":"R91","DOI":"10.1152\/ajpregu.00340.2004","article-title":"Programmed obesity in intrauterine growth-restricted newborns: modulation by newborn nutrition","volume":"288","author":"Desai","year":"2005","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"2021042608482726300_DEV131573C8","doi-asserted-by":"publisher","first-page":"1198","DOI":"10.1182\/blood-2006-02-004184","article-title":"Sox6 cell-autonomously stimulates erythroid cell survival, proliferation, and terminal maturation and is thereby an important enhancer of definitive erythropoiesis during mouse development","volume":"108","author":"Dumitriu","year":"2006","journal-title":"Blood"},{"key":"2021042608482726300_DEV131573C9","doi-asserted-by":"publisher","first-page":"1320","DOI":"10.2337\/db12-0289","article-title":"Metabolic programming of MEST DNA methylation by intrauterine exposure to gestational diabetes mellitus","volume":"62","author":"El Hajj","year":"2013","journal-title":"Diabetes"},{"key":"2021042608482726300_DEV131573C10","doi-asserted-by":"publisher","first-page":"1641","DOI":"10.1194\/jlr.M800590-JLR200","article-title":"Ontogeny and nutritional control of adipogenesis in zebrafish (Danio rerio)","volume":"50","author":"Flynn","year":"2009","journal-title":"J. Lipid Res."},{"key":"2021042608482726300_DEV131573C11","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/j.rbmo.2010.04.010","article-title":"Derivation efficiency, cell proliferation, freeze-thaw survival, stem-cell properties and differentiation of human Wharton's jelly stem cells","volume":"21","author":"Fong","year":"2010","journal-title":"Reprod. Biomed."},{"key":"2021042608482726300_DEV131573C12","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1079\/PHN2001145","article-title":"Fetal programming and adult health","volume":"4","author":"Godfrey","year":"2001","journal-title":"Public Health Nutr."},{"key":"2021042608482726300_DEV131573C13","doi-asserted-by":"publisher","first-page":"1528","DOI":"10.2337\/db10-0979","article-title":"Epigenetic gene promoter methylation at birth is associated with child's later adiposity","volume":"60","author":"Godfrey","year":"2011","journal-title":"Diabetes"},{"key":"2021042608482726300_DEV131573C14","doi-asserted-by":"publisher","first-page":"2062","DOI":"10.1002\/dvdy.21223","article-title":"Sox6 is required for normal fiber type differentiation of fetal skeletal muscle in mice","volume":"236","author":"Hagiwara","year":"2007","journal-title":"Dev. Dyn."},{"key":"2021042608482726300_DEV131573C15","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1152\/physrev.00029.2013","article-title":"Early developmental conditioning of later health and disease: physiology or pathophysiology?","volume":"94","author":"Hanson","year":"2014","journal-title":"Physiol. Rev."},{"key":"2021042608482726300_DEV131573C16","doi-asserted-by":"publisher","first-page":"37669","DOI":"10.1074\/jbc.M505392200","article-title":"SOX6 attenuates glucose-stimulated insulin secretion by repressing PDX1 transcriptional activity and is down-regulated in hyperinsulinemic obese mice","volume":"280","author":"Iguchi","year":"2005","journal-title":"J. Biol. Chem."},{"key":"2021042608482726300_DEV131573C17","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s13395-014-0026-2","article-title":"The role of Sox6 in zebrafish muscle fiber type specification","volume":"5","author":"Jackson","year":"2015","journal-title":"Skelet. Muscle"},{"key":"2021042608482726300_DEV131573C18","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1210\/me.2015-1020","article-title":"ACSL1 is associated with fetal programming of insulin sensitivity and cellular lipid content","volume":"29","author":"Joseph","year":"2015","journal-title":"Mol. Endocrinol."},{"key":"2021042608482726300_DEV131573C19","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1042\/BJ20101512","article-title":"Mest\/Peg1 inhibits WNT signalling through regulation of LRP6 glycosylation","volume":"436","author":"Jung","year":"2011","journal-title":"Biochem. J."},{"key":"2021042608482726300_DEV131573C20","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.febslet.2006.12.002","article-title":"Peg1\/Mest in obese adipose tissue is expressed from the paternal allele in an isoform-specific manner","volume":"581","author":"Kamei","year":"2007","journal-title":"FEBS Lett."},{"key":"2021042608482726300_DEV131573C21","doi-asserted-by":"publisher","first-page":"24004","DOI":"10.1074\/jbc.M501080200","article-title":"WNT signaling inhibits adipogenesis through beta-catenin-dependent and -independent mechanisms","volume":"280","author":"Kennell","year":"2005","journal-title":"J. Biol. Chem."},{"key":"2021042608482726300_DEV131573C22","doi-asserted-by":"publisher","first-page":"E365","DOI":"10.1152\/ajpendo.00599.2005","article-title":"Substrate-energy metabolism and metabolic risk factors for cardiovascular disease in relation to fetal growth and adult body composition","volume":"291","author":"Kensara","year":"2006","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"2021042608482726300_DEV131573C23","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1017\/S2040174414000178","article-title":"Association of early postnatal growth trajectory with body composition in term low birth weight infants","volume":"5","author":"Khandelwal","year":"2014","journal-title":"J. Dev. Orig. Health Dis."},{"key":"2021042608482726300_DEV131573C24","doi-asserted-by":"publisher","first-page":"1472","DOI":"10.1001\/archinte.160.10.1472","article-title":"Low birth weights contribute to the high rates of early-onset chronic renal failure in the southeastern United States","volume":"160","author":"Lackland","year":"2000","journal-title":"Arch. Intern. Med."},{"key":"2021042608482726300_DEV131573C25","doi-asserted-by":"publisher","first-page":"S69","DOI":"10.1053\/joca.2001.0447","article-title":"L-Sox5, Sox6 and Sox9 control essential steps of the chondrocyte differentiation pathway","volume":"9","author":"Lefebvre","year":"2001","journal-title":"Osteoarthritis Cartilage"},{"key":"2021042608482726300_DEV131573C26","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/j.tem.2014.04.001","article-title":"PPAR\u03b3 and the global map of adipogenesis and beyond","volume":"25","author":"Lefterova","year":"2014","journal-title":"Trends Endocrinol. Metab."},{"key":"2021042608482726300_DEV131573C27","doi-asserted-by":"publisher","first-page":"282","DOI":"10.5009\/gnl.2014.8.3.282","article-title":"Mest attenuates CCl4-induced liver fibrosis in rats by inhibiting the WNT\/\u03b2-catenin signaling pathway","volume":"8","author":"Li","year":"2014","journal-title":"Gut Liver"},{"key":"2021042608482726300_DEV131573C28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.mce.2009.07.031","article-title":"Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome","volume":"314","author":"Maury","year":"2010","journal-title":"Mol. Cell. Endocrinol."},{"key":"2021042608482726300_DEV131573C29","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1016\/S0140-6736(14)60460-8","article-title":"Global, regional, and national prevalence of overweight and obesity in children and adults during 1980\u20132013: a systematic analysis for the Global Burden of Disease Study 2013","volume":"384","author":"Ng","year":"2014","journal-title":"Lancet"},{"key":"2021042608482726300_DEV131573C30","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1101\/gad.948702","article-title":"C\/EBPalpha induces adipogenesis through PPARgamma: a unified pathway","volume":"16","author":"Rosen","year":"2002","journal-title":"Genes Dev."},{"key":"2021042608482726300_DEV131573C31","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1126\/science.289.5481.950","article-title":"Inhibition of adipogenesis by WNT signaling","volume":"289","author":"Ross","year":"2000","journal-title":"Science"},{"key":"2021042608482726300_DEV131573C32","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/S1534-5807(01)00003-X","article-title":"The transcription factors L-Sox5 and Sox6 are essential for cartilage formation","volume":"1","author":"Smits","year":"2001","journal-title":"Dev. Cell"},{"key":"2021042608482726300_DEV131573C33","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1038\/ijo.2013.193","article-title":"Newborns of obese parents have altered DNA methylation patterns at imprinted genes","volume":"39","author":"Soubry","year":"2015","journal-title":"Int. J. Obes."},{"key":"2021042608482726300_DEV131573C34","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1016\/j.devcel.2006.08.011","article-title":"SoxD proteins influence multiple stages of oligodendrocyte development and modulate SoxE protein function","volume":"11","author":"Stolt","year":"2006","journal-title":"Dev. Cell"},{"key":"2021042608482726300_DEV131573C35","doi-asserted-by":"publisher","first-page":"2287","DOI":"10.1093\/humrep\/deu209","article-title":"Molecular pathways reflecting poor intrauterine growth are found in Wharton's jelly-derived mesenchymal stem cells","volume":"29","author":"Sukarieh","year":"2014","journal-title":"Hum. Reprod."},{"key":"2021042608482726300_DEV131573C36","doi-asserted-by":"publisher","first-page":"E117","DOI":"10.1152\/ajpendo.00244.2004","article-title":"Mest\/Peg1 imprinted gene enlarges adipocytes and is a marker of adipocyte size","volume":"288","author":"Takahashi","year":"2005","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"2021042608482726300_DEV131573C37","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1530\/eje.1.02265","article-title":"Birth weight and risk of type 2 diabetes, abdominal obesity and hypertension among Chinese adults","volume":"155","author":"Tian","year":"2006","journal-title":"Eur. J. Endocrinol."},{"key":"2021042608482726300_DEV131573C38","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1038\/ijo.2014.34","article-title":"Epigenetics and human obesity","volume":"39","author":"van Dijk","year":"2015","journal-title":"Int. J. Obes."},{"key":"2021042608482726300_DEV131573C39","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1515\/JPEM.2010.23.3.215","article-title":"Intrauterine growth restriction as a potential risk factor for disease onset in adulthood","volume":"23","author":"Varvarigou","year":"2010","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"2021042608482726300_DEV131573C40","doi-asserted-by":"publisher","first-page":"37","DOI":"10.4137\/GEG.S18067","article-title":"Maternal stress, preterm birth, and DNA methylation at imprint regulatory sequences in humans","volume":"6","author":"Vidal","year":"2014","journal-title":"Genet. Epigenet."},{"key":"2021042608482726300_DEV131573C41","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/s12263-015-0477-z","article-title":"Identification of Mest\/Peg1 gene expression as a predictive biomarker of adipose tissue expansion sensitive to dietary anti-obesity interventions","volume":"10","author":"Voigt","year":"2015","journal-title":"Genes Nutr."}],"container-title":["Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1242\/dev.131573","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/dev\/article-pdf\/143\/6\/950\/1845336\/dev131573.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/dev\/article-pdf\/doi\/10.1242\/dev.131573\/2051991\/dev_131573v1.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/dev\/article-pdf\/doi\/10.1242\/dev.131573\/2051991\/dev_131573v1.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T17:08:33Z","timestamp":1621357713000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dev\/article\/doi\/10.1242\/dev.131573\/263948\/The-transcription-factor-SOX6-contributes-to-the"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,1,1]]},"references-count":41,"URL":"https:\/\/doi.org\/10.1242\/dev.131573","relation":{},"ISSN":["1477-9129","0950-1991"],"issn-type":[{"value":"1477-9129","type":"electronic"},{"value":"0950-1991","type":"print"}],"subject":[],"published":{"date-parts":[[2016,1,1]]},"article-number":"dev.131573"}}