Glossary
REV-ERB
REV-ERB alpha and beta are heme-sensing nuclear receptors that repress BMAL1 and tie the circadian clock to metabolism. Definition and research background.
The name REV-ERB covers two closely related nuclear receptors: REV-ERB alpha (NR1D1) and REV-ERB beta (NR1D2). They stand out within the receptor superfamily because they have no C-terminal helix 12, the element required to recruit coactivators, and so they can only act as repressors: with ligand bound, REV-ERB sits on ROR response elements and brings in the NCoR/HDAC3 complex. Their endogenous ligand is heme, turning them into direct sensors of the cell’s heme status.
The clock–metabolism link
Within the core circadian loop, REV-ERB suppresses Bmal1 transcription and counteracts the activating ROR receptors; the oscillation this creates sets the phase of clock-controlled genes further downstream. Since HDAC3 is also recruited to lipogenic and gluconeogenic promoters in the liver and to oxidative genes in muscle, REV-ERB provides one of the most direct molecular connections between circadian timing and metabolism.
The term shows up in research-compound catalogues because of synthetic agonists such as SR9009 (stenabolic) and SR9011. Accurate attribution matters: a study from 2019 found that SR9009 still has metabolic effects in cells completely lacking REV-ERB, so off-target activity is a central part of the current literature, not a side note. Related metabolic research focuses on PPAR-delta.
Related terms and material
AMPK · preclinical. Reference material: metabolic & circadian compounds. Further reading: what is SR9009 and cardarine vs SR9009.