bmal

Bmal, typically referring to BMAL1, is a transcription factor in the basic helix–loop–helix (bHLH) and PAS family that serves as a core component of the cellular circadian clock in mammals and other animals. The gene is commonly labeled ARNTL in humans.

BMAL1 forms a heterodimer with CLOCK (or NPAS2 in certain tissues). The BMAL1-CLOCK complex binds to E-box DNA sequences in the regulatory regions of clock genes, notably the Period (PER1–PER3) and Cryptochrome (CRY1–CRY2) families, activating their transcription. After accumulation, PER and CRY proteins feedback to repress BMAL1-CLOCK activity, generating a near-24-hour cycle of gene expression. This molecular clock drives rhythmic patterns in physiology, including sleep-wake cycles, hormone secretion, metabolism, and cellular processes. In mice, disruption of Bmal1 abolishes circadian rhythms and can cause metabolic and aging-related phenotypes; in humans, ARNTL variation has been linked to chronotype and susceptibility to metabolic disorders.

BMAL1 activity is modulated by post-translational modifications, including phosphorylation by kinases such as CK1δ/ε and GSK3β, and by metabolic cues that influence NAD+/SIRT1 signaling. Light information received by the retina entrains the central clock in the brain, which coordinates peripheral clocks through BMAL1-CLOCK activity, while peripheral tissues can maintain rhythms in a SCN-independent manner under certain conditions.

Beyond its clock role, BMAL1 participates in transcriptional networks controlling metabolism, DNA repair, and cell cycle progression, reflecting the integration of circadian timing with physiology.