Rev-erbα dynamically modulates chromatin looping to control circadian gene transcription

TY - JOUR

T1 - Rev-erbα dynamically modulates chromatin looping to control circadian gene transcription

AU - Kim, Yong Hoon

AU - Marhon, Sajid A

AU - Zhang, Yuxiang

AU - Steger, David J

AU - Won, Kyoung-Jae

AU - Lazar, Mitchell A

N1 - Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

PY - 2018/3/16

Y1 - 2018/3/16

N2 - Mammalian physiology exhibits 24-hour cyclicity due to circadian rhythms of gene expression controlled by transcription factors that constitute molecular clocks. Core clock transcription factors bind to the genome at enhancer sequences to regulate circadian gene expression, but not all binding sites are equally functional. We found that in mice, circadian gene expression in the liver is controlled by rhythmic chromatin interactions between enhancers and promoters. Rev-erba, a core repressive transcription factor of the clock, opposes functional loop formation between Rev-erba–regulated enhancers and circadian target gene promoters by recruitment of the NCoR- HDAC3 co-repressor complex, histone deacetylation, and eviction of the elongation factor BRD4 and the looping factor MED1. Thus, a repressive arm of the molecular clock operates by rhythmically modulating chromatin loops to control circadian gene transcription.

AB - Mammalian physiology exhibits 24-hour cyclicity due to circadian rhythms of gene expression controlled by transcription factors that constitute molecular clocks. Core clock transcription factors bind to the genome at enhancer sequences to regulate circadian gene expression, but not all binding sites are equally functional. We found that in mice, circadian gene expression in the liver is controlled by rhythmic chromatin interactions between enhancers and promoters. Rev-erba, a core repressive transcription factor of the clock, opposes functional loop formation between Rev-erba–regulated enhancers and circadian target gene promoters by recruitment of the NCoR- HDAC3 co-repressor complex, histone deacetylation, and eviction of the elongation factor BRD4 and the looping factor MED1. Thus, a repressive arm of the molecular clock operates by rhythmically modulating chromatin loops to control circadian gene transcription.

KW - Acetylation

KW - Animals

KW - Chromatin/chemistry

KW - Circadian Rhythm/genetics

KW - Enhancer Elements, Genetic

KW - Gene Expression Regulation

KW - Histone Deacetylases/metabolism

KW - Liver/metabolism

KW - Male

KW - Mediator Complex Subunit 1/metabolism

KW - Mice

KW - Mice, Knockout

KW - Nuclear Proteins/metabolism

KW - Nuclear Receptor Co-Repressor 1/metabolism

KW - Nuclear Receptor Subfamily 1, Group D, Member 1/genetics

KW - Promoter Regions, Genetic

KW - Protein Conformation

KW - Transcription Factors/metabolism

KW - Transcription, Genetic

U2 - 10.1126/science.aao6891

DO - 10.1126/science.aao6891

M3 - Journal article

C2 - 29439026

SN - 0036-8075

VL - 359

SP - 1274

EP - 1277

JO - Science (New York, N.Y.)

JF - Science (New York, N.Y.)

IS - 6381

ER -