Fig. 4

Circadian chromatin interactions in health and disease. a Many circadian long-range interactions direct enhancer-promoter contacts at a specific time of day and in a tissue-specific manner. For example, in the mouse liver, Cry1 promoter contacts an enhancer element located within an intron, specifically at ZT22 (night time). This interaction is characterized by H3K27ac mark at the enhancer (back dots), which is recognized by BRD4 and recruits the Mediator complex. eRNAs also appear at ZT22, and Cry1 gene is therefore transcribed. During the opposite phase, at ZT10 (day time), the clock protein REVERBα displaces Mediator and BRD4 from the enhancer region and recruits a repressor complex containing NCOR and the deacetylase HDAC3. The active enhancer marks H3K27ac and eRNA decrease and Cry1 transcription ceases [95]. b During the day, some chromatin interactions oscillate while others remain constant. Misalignment of circadian rhythms or certain pathological states could trigger different scenarios: circadian contacts could be disrupted leading, for example, to a permanent interaction of the absence of it (upper panel). Additionally, some new interactions may appear, either oscillatory or not (lower panel). These alterations may cause distinct patterns of gene expression as observed in certain pathological conditions, including cancer and cognitive or metabolic diseases