Michael C. Tackenberg, Kristina M. Heliodoro, Lily C. Melink, Yifan Liu, Kun Zhu, Mitchell A. Lazar. Normal circadian period length requires repression of Npas2 by REV-ERB nuclear receptors. Cell Reports, Volume 44, Issue 10, 2025, 116437, ISSN 2211-1247, https://doi.org/10.1016/j.celrep.2025.116437 (https://www.sciencedirect.com/science/article/pii/S2211124725012082)

Summary

REV-ERB nuclear receptors are integrated into the molecular circadian clock present in most mammalian cells. Loss of REV-ERBs (REV-ERB DKO) within the suprachiasmatic nucleus (SCN) in vivo leads to a marked shortening of the circadian period, but it remains unclear whether REV-ERB regulation of circadian period is tissue autonomous, if it is conserved across tissues, and how it is established. Here, we show that period shortening in the absence of REV-ERBs is tissue autonomous, is consistent between brain and liver, and is brought about through derepression of clock transcription factors NPAS2 and CLOCK. Thus, in addition to disruption of synchrony with the external environment, our results demonstrate that the circadian impacts of REV-ERB loss also include the alteration of core circadian properties with tissue-specific consequences.