Pre-established Chromatin Interactions Mediate the Genomic Response to Glucocorticoids.

TitlePre-established Chromatin Interactions Mediate the Genomic Response to Glucocorticoids.
Publication TypeJournal Article
Year of Publication2018
AuthorsAM D'Ippolito, IC McDowell, A Barrera, LK Hong, SM Leichter, LC Bartelt, CM Vockley, WH Majoros, A Safi, L Song, CA Gersbach, GE Crawford, and TE Reddy
JournalCell Systems
Volume7
Start Page146
Issue2
Pagination146 - 160.e7
Date Published08/2018
Abstract

The glucocorticoid receptor (GR) is a hormone-inducible transcription factor involved in metabolic and anti-inflammatory gene expression responses. To investigate what controls interactions between GR binding sites and their target genes, we used in situ Hi-C to generate high-resolution, genome-wide maps of chromatin interactions before and after glucocorticoid treatment. We found that GR binding to the genome typically does not cause new chromatin interactions to target genes but instead acts through chromatin interactions that already exist prior to hormone treatment. Both glucocorticoid-induced and glucocorticoid-repressed genes increased interactions with distal GR binding sites. In addition, while glucocorticoid-induced genes increased interactions with transcriptionally active chromosome compartments, glucocorticoid-repressed genes increased interactions with transcriptionally silent compartments. Lastly, while the architectural DNA-binding proteins CTCF and RAD21 were bound to most chromatin interactions, we found that glucocorticoid-responsive chromatin interactions were depleted for CTCF binding but enriched for RAD21. Together, these findings offer new insights into the mechanisms underlying GC-mediated gene activation and repression.

DOI10.1016/j.cels.2018.06.007
Short TitleCell Systems