Regulation of Rhythmic Transcription by CLOCK:BMAL1

Jerome S Menet, PhD

Department of Biology, Program of Genetics and Center for Biological Clocks Research

Texas A&M University

Abstract

Virtually every mammalian cell harbors a molecular circadian clock that enables biological functions to adapt to the daily variation of the environment. These clocks rely on the rhythmic recruitment of the heterodimeric transcription factor CLOCK:BMAL1 to its target genes promoter to coordinate the rhythmic expression of 10-15% of the transcriptome and promote the daily activation of key biochemical and metabolic pathways. The recent characterization of CLOCK:BMAL1 DNA binding sites at the genome-wide level has however revealed that the majority of CLOCK:BMAL1 target genes are not rhythmically expressed, suggesting that rhythmic CLOCK:BMAL1 DNA binding alone is not sufficient to activate rhythmic transcription. I will present our recent progress towards the identification of key mechanisms underlying the circadian regulation of rhythmic transcriptional output, focusing on the role of CLOCK:BMAL1-mediated chromatin remodeling and the cooperation of CLOCK:BMAL1 with other transcription factors. 

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