An intrinsically disordered region controlling condensation of a circadian clock component and rhythmic transcription in the liver. Mol Cell 2023 Oct 05;83(19):3457-3469.e7
Date
10/07/2023Pubmed ID
37802023Pubmed Central ID
PMC10575687DOI
10.1016/j.molcel.2023.09.010Scopus ID
2-s2.0-85172194127 (requires institutional sign-in at Scopus site) 30 CitationsAbstract
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.
Author List
Zhu K, Celwyn IJ, Guan D, Xiao Y, Wang X, Hu W, Jiang C, Cheng L, Casellas R, Lazar MAAuthor
Yang Xiao Assistant Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCircadian Clocks
Circadian Rhythm
Gene Expression
Liver
Mice
Nuclear Receptor Subfamily 1, Group D, Member 1
