Circadian transcriptional repressors REV-ERBα/β and E4BP4 regulate cardiac function

Sep 4, 2025Journal of molecular and cellular cardiology

Daily rhythm regulators REV-ERBα/β and E4BP4 control heart function

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Abstract

Circadian rhythms regulate many aspects of body physiology to maintain health.

Dysregulation of circadian rhythms is associated with diseases such as cancer and metabolic and cardiovascular disorders.
The circadian clock consists of a feedback loop involving activators like BMAL1 and CLOCK, and repressors such as REV-ERBα/β and E4BP4.
REV-ERBs and E4BP4 are implicated in regulating cardiac gene expression and metabolism.
These findings suggest potential therapeutic targets in REV-ERBs for treating cardiovascular disorders linked to circadian dysregulation.

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Circadian rhythms are an endogenous timekeeping system with a period of approximately 24 h that regulate many aspects of body physiology to maintain organismal health. Dysregulation of circadian rhythmicity has been implicated in various human diseases such as cancer as well as metabolic and cardiovascular disorders. Intrinsic, biological oscillations are regulated by the circadian clock, a molecular transcriptional/translational feedback loop that involves activators such as BMAL1 and CLOCK, and repressors such as REV-ERBα/β and E4BP4. Recent studies have shown that REV-ERBs and E4BP4 play a key role in regulating cardiac gene expression programs and metabolism. Here, we discuss these findings and highlight the mechanisms of their role in healthy and diseased hearts. Since REV-ERBs are drug targets, they hold potential for the treatment of cardiovascular disorders that are linked to circadian dysregulation or metabolic imbalance.