A day in the life of chromatin: how enhancer–promoter loops shape daily behavior

Abstract

Each spring, we get out of bed 1 h ahead of our biological wake-up time due to the misalignment of internal clocks with the light–dark cycle. Genetic discoveries revealed that clock genes encode transcription factors that are expressed throughout many tissues, yet a gap has remained in understanding the temporal dynamics of transcription. Two groups now apply circular chromosome conformation capture and high-throughput sequencing to dissect how “time of day”-dependent changes in chromatin drive core clock oscillations. A surprise is the finding that disruption of enhancer–promoter contacts within chromatin leads to an advance in the “wake-up” time of mice. Furthermore, the assembly of transcriptionally active domains of chromatin requires the ordered recruitment of core clock transcription factors each day. These studies show that waking up involves highly dynamic changes in the three-dimensional positioning of genes within the cell.