ReportGene Regulation

Discrete functions of nuclear receptor Rev-erbα couple metabolism to the clock

Science  04 Jun 2015:

DOI: 10.1126/science.aab3021

You are currently viewing the abstract.

View Full Text

Via your Institution

Log in through your institution

Log in through your institution


Abstract

Circadian and metabolic physiology are intricately intertwined, as illustrated by Rev-erbα, 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-erbα modulates the clock and metabolism by different genomic mechanisms. Clock control requires Rev-erbα to bind directly to the genome at its cognate sites, where it competes with activating ROR TFs. By contrast, Rev-erbα 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-erbα and ROR TFs provides a universal mechanism for self-sustained control of molecular clock across all tissues, whereas Rev-erbα utilizes lineage-determining factors to convey a tissue-specific epigenomic rhythm that regulates metabolism tailored to the specific need of that tissue.‬‬‬‬

View Full Text

Related Content