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Publication : Histone monoubiquitination by Clock-Bmal1 complex marks Per1 and Per2 genes for circadian feedback.

First Author  Tamayo AG Year  2015
Journal  Nat Struct Mol Biol Volume  22
Issue  10 Pages  759-66
PubMed ID  26323038 Mgi Jnum  J:245381
Mgi Id  MGI:5919179 Doi  10.1038/nsmb.3076
Citation  Tamayo AG, et al. (2015) Histone monoubiquitination by Clock-Bmal1 complex marks Per1 and Per2 genes for circadian feedback. Nat Struct Mol Biol 22(10):759-66
abstractText  Circadian rhythms in mammals are driven by a feedback loop in which the transcription factor Clock-Bmal1 activates expression of Per and Cry proteins, which together form a large nuclear complex (Per complex) that represses Clock-Bmal1 activity. We found that mouse Clock-Bmal1 recruits the Ddb1-Cullin-4 ubiquitin ligase to Per (Per1 and Per2), Cry (Cry1 and Cry2) and other circadian target genes. Histone H2B monoubiquitination at Per genes was rhythmic and depended on Bmal1, Ddb1 and Cullin-4a. Depletion of Ddb1-Cullin-4a or an independent decrease in H2B monoubiquitination caused defective circadian feedback and decreased the association of the Per complex with DNA-bound Clock-Bmal1. Clock-Bmal1 thus covalently marks Per genes for subsequent recruitment of the Per complex. Our results reveal a chromatin-mediated signal from the positive to the negative limb of the clock that provides a licensing mechanism for circadian feedback.
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