An Intrinsic Disorder Region Controlling Condensation of a Circadian Clock Component and Rhythmic Transcription in the Liver [ChIA-PET]
Circadian gene transcription is fundamental to metabolic physiology. Here we report that the nuclear receptor REV-ERBalpha, 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-ERBalpha 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-ERBalpha. This work demonstrates physiological circadian protein condensates containing REV-ERBalpha  whose IDR is required for hub formation and the control of rhythmic gene expression. Overall design: In-situ Chromatin Interaction Analysis with Paired-End Tag (In-situ ChIA-PET) for REV-ERBalpha  at different circadian time points (ZT22/ZT10) or different AAV virus combinational injection (DKO+WT, DKO+?hIDR)