Unknown,Transcriptomics,Genomics,Proteomics

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HNF4A is required to specify glucocorticoid action in the liver - ATACseq

ABSTRACT: The glucocorticoid receptor (GR) is a nuclear hormone receptor critical to the regulation of energy metabolism and the inflammatory response. The actions of GR are highly dependent on cell type and environmental context. Here, we demonstrate the necessity for liver lineage-determining factor hepatocyte nuclear factor 4A (HNF4A) in defining liver-specificity of GR action. In normal mouse liver, the HNF4 motif lies adjacent to the glucocorticoid response element (GRE) at GR binding sites found within regions of open chromatin. In the absence of HNF4A, the liver GR cistrome is remodelled, with both loss and gain of GR recruitment evident. Loss of chromatin accessibility at HNF4A-marked sites leads to loss of GR binding at weak GRE motifs. GR binding is gained at sites characterised by strong GRE motifs, which typically show GR recruitment in non-liver tissues. The functional importance of these HNF4A-regulated GR sites is further demonstrated by evidence of an altered transcriptional response to glucocorticoid treatment in the Hnf4a-null liver.

INSTRUMENT(S): Illumina HiSeq 4000, NextSeq 500

ORGANISM(S): Mus musculus

SUBMITTER: Rachel Scholey

PROVIDER: E-MTAB-10266 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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HNF4A is required to specify glucocorticoid action in the liver - ATACseq

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