ChIP-Seq on ESR1 in human liver tissue and hepatocytes

To improve our understanding of transcriptional regulation by ESR1 in the liver, chromatin immunoprecipitation with an antibody against ESR1 followed by high-throughput sequencing (ESR1 ChIP-Seq) was conducted in human liver samples and in hepatocytes with or without 17beta-estradiol (E2) treatment. By comparing treated and untreated hepatocytes, we identified both ligand-dependent and ligand-independent binding sites throughout the genome. Ligand-dependent binding sites include ChIP-Seq peaks that either appeared (gained peaks) or disappeared (lost peaks) upon estrogen treatment. Gained peaks occurred at the Estrogen Response Element (ERE) whereas the sites for lost peaks were instead coenriched with a variety of transcription factors. In both cases, ESR1 binding primarily occurred in enhancer regions and was associated with general liver functions, such as lipid/energy metabolism. In contrast, we also observed a subset of ESR1 sites that were maintained regardless of estrogen treatment. These ligand-independent sites mostly occurred at promoter regions and were highly enriched with several cofactor motifs. Overall design: ESR1 chromatin binding was examined in human liver and hepatocytes with and without estradiol treatment