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

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 have been shown to be highly dependent on context. Here, we demonstrate the necessity for liver lineage-determining factor hepatocyte nuclear factor 4A (HNF4A) in defining tissue-specificity of GR action. In normal 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. Lost sites are characterised by HNF4 motifs and weak GRE motifs. Gained sites are characterised by strong GRE motifs, and typically show GR recruitment in non-liver tissues. These RNA-seq data demonstrate the functional importance of these HNF4A-regulated GR sites by showing evidence of an altered transcriptional response to glucocorticoid treatment in the Hnf4a-null liver. In Hnf6-null liver, a far more minor effect on the glucocorticoid response is observed.

INSTRUMENT(S): Illumina HiSeq 4000

ORGANISM(S): Mus musculus

SUBMITTER: Rachel Scholey 

PROVIDER: E-MTAB-10247 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress