Glucocorticoid receptor regulates the ANGPTL4 gene in a CTCF-mediated chromatin context in human hepatic cells

Glucocorticoid plays an essential role in various stress responses and metabolism, which is mediated by the glucocorticoid receptor (GR) in cells. This hormonal action is integrated to transcriptional control of the GR target genes in cell type-specific and condition-dependent manners. In this study, we report that GR regulates the angiopoietin-like 4 (ANGPTL4) gene in a CCCTC-binding factor (CTCF)-mediated chromatin context in human hepatic HepG2 cells. There were at least four CTCF-enriched sites and two GR-binding sites in the ANGPTL4 locus. Among them, major CTCF-enriched site was positioned nearly GR-bound enhancer of this gene. Using treatment with the synthetic glucocorticoid dexamethasone (Dex), our data showed that CTCF is required for proper induction and subsequent silencing of ANGPTL4 gene. Interestingly, this gene induction was diminished under the long-term Dex pretreatment. Although ANGPTL4 locus maintains stable higher-order chromatin conformation at the basal and the Dex-treated states, liganded GR activated the ANGPTL4 gene, but not the neighboring three genes, via the interactions between enhancer, promoter and CTCF sites. These results reveal that liganded GR spatiotemporally controls ANGPTL4 gene in the chromosomal context. Overall design: In total 2 samples; 1 input sample and 1 ChIP-seq sample