An Intrinsically Disordered Region Controlling Condensation of a Circadian Clock Component and Rhythmic Transcription in the Liver

Authors

Kun Zhu
Isaac J Celwyn
Dongyin Guan
Yang Xiao
Xiang Wang
Wenxiang Hu
Chunjie Jiang
Lan Cheng
Rafael Casellas
Mitchell A Lazar

Publication Date

10-5-2023

Journal

Molecular Cell

DOI

10.1016/j.molcel.2023.09.010

PMID

37802023

PMCID

PMC10575687

PubMedCentral® Posted Date

10-5-2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Mice, Animals, Circadian Clocks, Circadian Rhythm, Nuclear Receptor Subfamily 1, Group D, Member 1, Liver, Gene Expression

Abstract

Circadian gene transcription is fundamental to metabolic physiology. Here we report that the nuclear receptor REV-ERBα, a repressive component of the molecular clock, forms circadian condensates in the nuclei of mouse liver. These condensates are dictated by an intrinsically disordered region (IDR) located in the protein's hinge region which specifically concentrates nuclear receptor corepressor 1 (NCOR1) at the genome. IDR deletion diminishes the recruitment of NCOR1 and disrupts rhythmic gene transcription in vivo. REV-ERBα condensates are located at high-order transcriptional repressive hubs in the liver genome that are highly correlated with circadian gene repression. Deletion of the IDR disrupts transcriptional repressive hubs and diminishes silencing of target genes by REV-ERBα. This work demonstrates physiological circadian protein condensates containing REV-ERBα whose IDR is required for hub formation and the control of rhythmic gene expression.

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