GSE178168
Genome-wide ChIPseq analysis of COUP-TFII, and HNF4a following 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-treatment in mouse liver
Treatment of mice with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been shown to disrupt many physiological processes including hepatic lipid metabolism, bile acid homeostasis, glucose metabolism, iron and heme homeostasis, and one-carbon metabolism. TCDD disrupts these metabolic pathways mediated by the aryl hydrocarbon receptor (AhR). We have previously shown that the AhR localizes to genomic regions possessing DNA motifs that also contain binding sites for other transcription factors, implicating potential co-operation between the AhR and these other transcription factors in the regulation of target genes. Two possible co-operating transcription factors include HNF4a and COUP-TFII. To investigate interactions between AhR, HNF4a and COUP-TFII hepatic ChIP-seq analysis was performed for HNF4a and COUP-TFII mice treated with TCDD for 2 hours, to supplement pre-existing AhR ChIP-seq data. ChIP-seq analysis revealed genome-wide changes in COUP-TFII and HNF4a binding following treatment with TCDD, with 11,688 and 9,547 genomic regions possessing differential enrichment, respectively. These differentially enriched regions for COUP-TFII and HNF4a fell within the intragenic region of 6,846 and 5,762 genes, respectively. When supplemented with pre-existing AhR ChIP-seq data, AhR, HNF4a and COUP-TFII were found to co-bind to the intragenic region of 6,376 genes. Overall design: Five biological replicates, pooled