The RelB subunit of NFκB acts as a negative regulator of circadian gene expression.
The circadian system controls a large array of physiological and metabolic functions. The molecular organization of the circadian clock is complex, involving various elements organized in feedback regulatory loops. Here we demonstrate that the RelB subunit of NFκB acts as a repressor of circadian transcription. RelB physically interacts with the circadian activator BMAL1 in the presence of CLOCK to repress circadian gene expression at the promoter of the clock-controlled gene Dbp. The repression is independent of the circadian negative regulator CRY. Notably, RelB -/- fibroblasts have profound alterations of circadian genes expression. These findings reveal a previously unforeseen function for RelB as an important regulator of the mammalian circadian system in fibroblasts.
Center for Epigenetics and Metabolism, School of Medicine, University of California, Irvine, Irvine, CA, USA.
Marina M
MM
Bellet
Loredana
L
Zocchi
Paolo
P
Sassone-Corsi
D056930:ARNTL Transcription Factors / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D056926:CLOCK Proteins / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D055786:Gene Knockout Techniques; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051841:Transcription Factor RelB / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics / Q000502:physiology*
D056930:ARNTL Transcription Factors; C538960:BMAL1 protein, human; D017931:DNA Primers; C497593:RELB protein, human; D051841:Transcription Factor RelB; D056926:CLOCK Proteins; C538943:CLOCK protein, human