Histone monoubiquitination by Clock-Bmal1 complex marks Per1 and Per2 genes for circadian feedback.
Histone monoubiquitination by Clock-Bmal1 complex marks Per1 and Per2 genes for circadian feedback.
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DOI：
10.1038/nsmb.3076
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发表时间：
2015-10
影响因子：
16.8
通讯作者：
Weitz CJ
中科院分区：
文献类型：
--
作者：
Tamayo AG;Duong HA;Robles MS;Mann M;Weitz CJ
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, Cry, and other circadian target genes. Histone 2B mono-ubiquitination at Per genes was rhythmic and depended on Bmal1, Ddb1, and Cullin-4a. Depletion of Ddb1–Cullin-4a or independent reduction of Histone 2B mono-ubiquitination caused defective circadian feedback and reduced 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.
