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E47 modulates hepatic glucocorticoid action

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Item Type:Article
Title:E47 modulates hepatic glucocorticoid action
Creators Name:Hemmer, M.C. and Wierer, M. and Schachtrup, K. and Downes, M. and Hübner, N. and Evans, R.M. and Uhlenhaut, N.H.
Abstract:Glucocorticoids (GCs) are effective drugs, but their clinical use is compromised by severe side effects including hyperglycemia, hyperlipidemia and obesity. They bind to the Glucocorticoid Receptor (GR), which acts as a transcription factor. The activation of metabolic genes by GR is thought to underlie these adverse effects. We identify the bHLH factor E47 as a modulator of GR target genes. Using mouse genetics, we find that E47 is required for the regulation of hepatic glucose and lipid metabolism by GR, and that loss of E47 prevents the development of hyperglycemia and hepatic steatosis in response to GCs. Here we show that E47 and GR co-occupy metabolic promoters and enhancers. E47 is needed for the efficient recruitment of GR and coregulators such as Mediator to chromatin. Altogether, our results illustrate how GR and E47 regulate hepatic metabolism, and might provide an entry point for novel therapies with reduced side effects.
Keywords:Chromatin Immunoprecipitation, Fatty Liver, Gene Expression Profiling, Glucocorticoids, Glucose, Lipid Metabolism, Liver, Glucocorticoid, Receptors, Transcription Factor 3 Transcription Factor 3, Mice, Knockout, Animals
Source:Nature Communications
ISSN:2041-1723
Publisher:Nature Publishing Group (U.K.)
Volume:10
Number:1
Page Range:306
Date:18 January 2019
Official Publication:https://doi.org/10.1038/s41467-018-08196-5
PubMed:View item in PubMed

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