Kang, SonaTsai, LinusZhou, YimingEvertts, AdamXu, SuGriffin, Michael J.Issner, RobbynWhitton, Holly J.Garcia, Benjamin A.Epstein, Charles B.Mikkelsen, Tarjei S.Rosen, Evan2015-08-032014Kang, S., L. T. Tsai, Y. Zhou, A. Evertts, S. Xu, M. J. Griffin, R. Issner, et al. 2014. “Identification of nuclear hormone receptor pathways causing insulin resistance by transcriptional and epigenomic analysis.” Nature cell biology 17 (1): 44-56. doi:10.1038/ncb3080. http://dx.doi.org/10.1038/ncb3080.1465-7392http://nrs.harvard.edu/urn-3:HUL.InstRepos:17820822Summary Insulin resistance is a sine qua non of Type 2 diabetes (T2D) and a frequent complication of multiple clinical conditions, including obesity, aging, and steroid use, among others. How such a panoply of insults can result in a common phenotype is incompletely understood. Furthermore, very little is known about the transcriptional and epigenetic basis of this disorder, despite evidence that such pathways are likely to play a fundamental role. Here, we compare cell autonomous models of insulin resistance induced by the cytokine tumor necrosis factor-α (TNF) or by the steroid dexamethasone (Dex) to construct detailed transcriptional and epigenomic maps associated with cellular insulin resistance. These data predict that the glucocorticoid receptor and vitamin D receptor are common mediators of insulin resistance, which we validate using gain- and loss-of-function studies. These studies define a common transcriptional and epigenomic signature in cellular insulin resistance enabling the identification of pathogenic mechanisms.en-USJournal Article2015-08-0310.1038/ncb3080