Orateur
Description
Mammalian circadian oscillators are built on a feedback loop where the activity of the transcription factor CLOCK:BMAL1 is repressed by the PER-CRY complex. We found that Per deficient cells displayed altered nucleosome occupancy around transcription start sites (TSS) and at promoter-proximal and distal CTCF sites in the genome. This chromatin re-organization was coincident with a significant decrease in histone variant H2A.Z deposition, a process that is reversed by re-expressing mPer2. Knocking out H2A.Z altered nucleosome occupancy at clock promoters, TSS and CTCF sites and thus mimicked Per loss. H2A.Z deletion furthermore completely disrupted cellular rhythms. Our work implicates a PER-H2A.Z network hub at the core of the circadian oscillator regulating not just the establishment of the clock mechanism but also its outputs and genome organization. Thus, physio-pathological scenarios where H2A.Z is mis-expressed, or its deposition dynamics, recognition or function are mis-regulated, could potentially also be compromised for circadian function.
