Help from my friends-cooperation of BMAL1 with noncircadian transcription factors

Abstract

The circadian clock in the suprachiasmatic nucleus (SCN) of mammals drives 24-h rhythms of sleep/wake cycles. Peripheral clocks present in other organs coordinate local and global physiology according to rhythmic signals from the SCN and via metabolic cues. The core circadian clockwork is identical in all cells. However, there is only a small amount of overlap of the circadian transcriptomes in different organs and tissues. A novel study by Beytebiere and colleagues (pp. 294-309) indicates that the regulation of tissue-specific rhythmic gene expression involves the cooperation of the circadian transcription factor (TF) BMAL1:CLOCK with tissue-specific TFs (ts-TFs) and correlates with the potential of BMAL1:CLOCK to facilitate rhythmic enhancer-enhancer interactions.

Keywords: circadian clock; enhancer–enhancer interactions; tissue-specific cistromes; transcription.

Figure 1.

Model of interaction of BMAL1:CLOCK with noncircadian transcription factors. (A) Schematic of Pol II ChIA-PET. A DHS with binding sites for BMAL1:CLOCK (blue box) and the hypothetical noncircadian transcription factor X (red box) interacts with the transcription start site (TSS) of the gene, and both interact in addition with a gene-specific DHS with a binding site for the noncircadian transcription factor Y (green box). (B) Nucleosome-mediated cooperativity of BMAL1/CLOCK (BMAL1) with X and Y. BMAL1, X, and Y are required to mutually facilitate their recruitment by depleting nucleosomes (gray octamers) from their binding sites. Rhythmic binding of BMAL1 synergistically supports rhythmic recruitment of the noncircadian TFs X and Y and thereby supports high expression levels and high-amplitude rhythms. (C) X and Y bind independently of BMAL1. The rhythmic contribution of BMAL1 is blunted in presence of X and Y.