Abstract
Circadian rhythms in transcription are generated by rhythmic abundances and DNA binding activities of transcription factors. Propagation of rhythms to transcriptional initiation involves the core promoter, its chromatin state, and the basal transcription machinery. Here, I characterize core promoters and chromatin states of genes transcribed in a circadian manner in mouse liver and in Drosophila. It is shown that the core promoter is a critical determinant of circadian mRNA expression in both species. A distinct core promoter class, strong circadian promoters (SCPs), is identified in mouse liver but not Drosophila. SCPs are defined by specific core promoter features, and are shown to drive circadian transcriptional activities with both high averages and high amplitudes. Data analysis and mathematical modeling further provided evidence for rhythmic regulation of both polymerase II recruitment and pause release at SCPs. The analysis provides a comprehensive and systematic view of core promoters and their link to circadian mRNA expression in mouse and Drosophila, and thus reveals a crucial role for the core promoter in regulated, dynamic transcription.
Highlights
In many metazoans, transcription of numerous genes in most cell types occurs in a rhythmic fashion with a period of ~24 hours, if the organism is held under constant conditions; these rhythms are termed circadian transcriptional rhythms [1]
There is a layer between transcription factor action and transcriptional activity whose role in circadian transcription has not previously been characterized: the core promoter
There are different types of core promoters that are typically used for different types of genes
Summary
Transcription of numerous genes in most cell types occurs in a rhythmic fashion with a period of ~24 hours, if the organism is held under constant conditions; these rhythms are termed circadian transcriptional rhythms [1] They are to a large extent orchestrated by the cellular circadian clock, which consists of connected feedback loops of clock genes that code for clock proteins. In the fly Drosophila melanogaster, the CLOCK homolog CLK has a similar function, binding to E-boxes [8] Rhythmic binding of these core circadian clock TFs (CTFs) and their coregulators to promoters are thought to induce rhythms in transcriptional activities, which lead to rhythms in mRNA and protein abundances
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