HNF4A modulates glucocorticoid action in the liver.

Abstract

The glucocorticoid receptor (GR) is a nuclear receptor critical to the regulation of energy metabolism and inflammation. The actions of GR are dependent on cell type and context. Here, we demonstrate the role of liver lineage-determining factor hepatocyte nuclear factor 4A (HNF4A) in defining liver specificity of GR action. In mouse liver, the HNF4A motif lies adjacent to the glucocorticoid response element (GRE) at GR binding sites within regions of open chromatin. In the absence of HNF4A, the liver GR cistrome is remodeled, with loss and gain of GR recruitment evident. Loss of chromatin accessibility at HNF4A-marked sites associates with loss of GR binding at weak GRE motifs. GR binding and chromatin accessibility are gained at sites characterized by strong GRE motifs, which show GR recruitment in non-liver tissues. The functional importance of these HNF4A-regulated GR sites is indicated by an altered transcriptional response to glucocorticoid treatment in the Hnf4a-null liver.

• Authors: A Louise Hunter, Toryn M Poolman, Donghwan Kim, Frank J Gonzalez, David A Bechtold, Andrew S I Loudon, Mudassar Iqbal, David W Ray
• Journal: Cell reports (Cell Rep) Vol. 39 Issue 3 Pg. 110697 (04 19 2022) ISSN: 2211-1247 [Electronic] United States
• PMID: 35443180 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

Chemical References

• Chromatin
• Glucocorticoids
• Hepatocyte Nuclear Factor 4
• Hepatocyte Nuclear Factors
• Hnf4a protein, mouse
• Receptors, Glucocorticoid

Topics

• Animals
• Chromatin (metabolism)
• Glucocorticoids (metabolism, pharmacology)
• Hepatocyte Nuclear Factor 4 (genetics, metabolism)
• Hepatocyte Nuclear Factors (metabolism)
• Liver (metabolism)
• Mice
• Receptors, Glucocorticoid (metabolism)