GSE67962
Discrete Functions of Rev-erba Couple Metabolism to the Clock [HTS]
Circadian and metabolic physiology are intricately intertwined, as illustrated by Rev-erb , a transcription factor (TF) that functions both as a core repressive component of the cell autonomous clock and as a regulator of metabolic genes.  Here we show that Rev-erb  modulates the clock and metabolism by different genomic mechanisms. Clock control requires Rev-erb  to bind directly to the genome at its cognate sites, where it competes with activating ROR TFs. By contrast, Rev-erb  regulates metabolic genes primarily by recruiting the HDAC3 corepressor to sites to which it is tethered by cell type-specific transcription factors.  Thus, direct competition between Rev-erb  and ROR TFs provides a universal mechanism for self-sustained control of molecular clock across all tissues, whereas Rev-erb  utilizes lineage-determining factors to convey a tissue-specific epigenomic rhythm that regulates metabolism tailored to the specific need of that tissue. Overall design: Biological replicates were uploaded in separated files and indicated in the file names.