Proteomics

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Twenty-four hour rhythms in the absence of the clock gene Bmal1


ABSTRACT: Circadian (~24 hour) clocks exist in almost all types of living organism and play a fundamental role in regulating daily physiological and behavioural processes. The transcription factor BMAL1 (ARNTL) is thought to be one of the principal drivers of the molecular clock in mammals since its deletion abolishes 24-hour activity patterning, an important physiological output of the clockwork. However, whether or not Bmal1-/- mice can nevertheless display molecular 24-hour rhythms is unknown. Here, we determined whether Bmal1 function is necessary for daily molecular oscillations in two tissues – skin fibroblasts and liver. Unexpectedly, both tissues exhibited robust 24-hour oscillations over 2-3 days in the absence of any exogenous synchronizers such as daily light or temperature cycles. This demonstrates a competent 24-hour molecular pacemaker in Bmal1 knockouts. Indeed, molecular oscillations were pervasive throughout the transcriptome, proteome and phosphoproteome of Bmal1-/- mice. In particular, several proteins exhibited rhythmic phosphorylation in both Bmal1-proficient and -deficient cells, highlighting an unanticipated role for post-translational regulators in 24-hour rhythms in the absence of any known clock mechanisms.

INSTRUMENT(S): Orbitrap Fusion Lumos, Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Liver, Skin, Fibroblast

SUBMITTER: Sandipan Ray  

LAB HEAD: Akhilesh B. Reddy

PROVIDER: PXD009243 | Pride | 2020-02-17

REPOSITORIES: pride

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Publications

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

Ray Sandipan S   Valekunja Utham K UK   Stangherlin Alessandra A   Howell Steven A SA   Snijders Ambrosius P AP   Damodaran Gopinath G   Reddy Akhilesh B AB  

Science (New York, N.Y.) 20200201 6479


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, p  ...[more]

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