Circadian rhythms in the absence of the clock gene Bmal1.

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. Bmal1 deletion abolishes 24-hour activity patterning, one measure of clock output. We determined whether Bmal1 function is necessary for daily molecular oscillations in skin fibroblasts and liver slices. Unexpectedly, in Bmal1 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 Bmal1 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.