Circadian rhythms in the absence of the clock gene <i>Bmal1</i>.

Abstract

Circadian (~24 hour) clocks have a fundamental role in regulating daily physiology. The transcription factor BMAL1 is a principal driver of a molecular clock in mammals. <i>Bmal1</i> deletion abolishes 24-hour activity patterning, one measure of clock output. We determined whether <i>Bmal1</i> function is necessary for daily molecular oscillations in skin fibroblasts and liver slices. Unexpectedly, in <i>Bmal1</i> knockout mice, both tissues exhibited 24-hour oscillations of the transcriptome, proteome, and phosphoproteome over 2 to 3 days in the absence of any exogenous drivers such as daily light or temperature cycles. This demonstrates a competent 24-hour molecular pacemaker in <i>Bmal1</i> knockouts. We suggest that such oscillations might be underpinned by transcriptional regulation by the recruitment of ETS family transcription factors, and nontranscriptionally by co-opting redox oscillations.