Year: 2022
Type: article
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.
Source: Cell Reports
Language: English
Subfield: Endocrinology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,200
Awards: REVing-down: targeting the circadian clock in metabolic disease, Clock control of inflammation in the lung., Inflammatory therapeutics and the role of the circadian clock, Clock control of inflammation in the lung., Advancing therapeutics by exploiting single cell functional analysis, Inflammatory therapeutics and the role of the circadian clock, G6312036920, Elucidating clock control of glucocorticoid action, G6868616705, Clock control of inflammation in the lung.
OpenAlex ID: W4224217744