GENE REGULATION. Discrete functions of nuclear receptor Rev-erb? couple metabolism to the clock.

ABSTRACT: 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 co-repressor 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 the molecular clock across all tissues, whereas Rev-erb? uses lineage-determining factors to convey a tissue-specific epigenomic rhythm that regulates metabolism tailored to the specific need of that tissue.

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC4613749 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature