Identification of nuclear hormone receptor pathways causing insulin resistance by transcriptional and epigenomic analysis

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Author
Zhou, Yiming
Evertts, Adam
Xu, Su
Griffin, Michael J.
Issner, Robbyn
Whitton, Holly J.
Garcia, Benjamin A.
Epstein, Charles B.
Mikkelsen, Tarjei S.
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1038/ncb3080Metadata
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Kang, 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.Abstract
Summary 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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4281178/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:17820822
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