Clock-dependent chromatin topology modulates circadian transcription and behavior

摘要: The circadian clock in animals orchestrates widespread oscillatory gene expression programs, which underlie 24-h rhythms behavior and physiology. Several studies have shown the possible roles of transcription factors chromatin marks controlling cyclic expression. However, how daily active enhancers modulate rhythmic mammalian tissues is not known. Using circular chromosome conformation capture (4C) combined with sequencing (4C-seq), we discovered promoter-enhancer interactions along cycle mouse liver kidney. Rhythms were abolished arrhythmic Bmal1 knockout mice. Deleting a contacted intronic enhancer element Cryptochrome 1 ( Cry1 ) was sufficient to compromise contacts tissues. Moreover, deletion reduced dynamics transcriptional burst frequency and, remarkably, shortened period locomotor activity rhythms. Our results establish oscillating clock-controlled looping as regulatory layer underlying behavior.