Pre-established Chromatin Interactions Mediate the Genomic Response to Glucocorticoids

Cell Systems
Anthony M D'IppolitoTimothy E Reddy

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 activatio...Continue Reading

Citations

May 31, 2019·Nature Reviews. Molecular Cell Biology·Adrian Pickar-Oliver, Charles A Gersbach
Jun 3, 2020·Integrative and Comparative Biology·Richard G Hunter
Sep 18, 2020·Nucleic Acids Research·Yuliang Feng, Siim Pauklin
Dec 24, 2018·Nature Communications·Graham D JohnsonTimothy E Reddy
Mar 15, 2019·Life Science Alliance·Verena ThormannSebastiaan H Meijsing
Jan 10, 2021·Nature Cell Biology·Muneaki NakamuraLei S Qi
Jan 17, 2021·Protein & Cell·Yuliang FengSiim Pauklin
Nov 3, 2020·Frontiers in Endocrinology·Stine M PræstholmLars Grøntved
Mar 16, 2019·Current Opinion in Cell Biology·Dahong Chen, Elissa P Lei
Mar 7, 2021·Genome Research·Jungkyun SeoTimothy E Reddy
May 1, 2021·International Journal of Molecular Sciences·Malgorzata BorczykMarcin Piechota
May 17, 2019·Genomics·Elsie C JacobsonJustin M O'Sullivan
Aug 28, 2021·Life Science Alliance·Melissa BotheSebastiaan H Meijsing

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