Temporal orchestration of repressive chromatin modifiers by circadian clock Period complexes.
Temporal orchestration of repressive chromatin modifiers by circadian clock Period complexes.
复制标题
DOI：
10.1038/nsmb.2746
复制
发表时间：
2014-02
影响因子：
16.8
通讯作者：
Weitz CJ
中科院分区：
文献类型：
--
作者：
Duong HA;Weitz CJ
哺乳动物的生物钟是建立在一个分子反馈环上的，在这个环中，周期蛋白(PER)在一个大型的、鲜为人知的复合体中作用，抑制驱动它们表达的转录因子BMAL1。我们发现小鼠PER复合体中含有组蛋白甲基转移酶Hp1γ-Suv39H。PER蛋白将HP1Suv39H招募到PER1和PER2启动子上，HP1Suv39H对组蛋白-3赖氨酸-9(H3K9)在PER1启动子上的二甲基化和三甲基化、反馈转录抑制和生物钟功能起重要作用。Hp1γ-Suv39H在HDAC1后约4小时被招募到PER1和PER2启动子中，HDAC1是一种与时钟功能和PER1启动子上的H3K9去乙酰化有关的PER相关蛋白。根据PER，含有HDAC1或HP1Suv39H的γ-Suv39H似乎是物理上可分离的。因此，PER复合体的昼夜时钟负反馈涉及到动态、有序地将抑制性染色质修饰物重新招募到DNA结合的时钟BMAL1。
The mammalian circadian clock is built on a molecular feedback loop in which the PERIOD (PER) proteins, acting in a large, poorly-understood complex, repress CLOCK-BMAL1, the transcription factor driving their expression. We found that mouse PER complexes include the histone methyltransferase HP1γ-Suv39H. PER proteins recruit HP1γ-Suv39H to the Per1 and Per2 promoters, and HP1γ-Suv39H proved important for circadian di- and tri-methylation of histone-3 lysine-9 (H3K9) at the Per1 promoter, feedback transcriptional repression, and circadian clock function. HP1γ-Suv39H was recruited to the Per1 and Per2 promoters ~4 hours after HDAC1, a PER-associated protein we previously implicated in clock function and H3K9 deacetylation at the Per1 promoter. PER complexes containing HDAC1 or HP1γ-Suv39H appeared to be physically separable. Circadian clock negative feedback by the PER complex thus involves dynamic, ordered recruitment of repressive chromatin modifiers to DNA-bound CLOCK-BMAL1.
登录
查看更多内容
影响因子：
14.9
作者：
Choi JD;Park MA;Lee JS
通讯作者：
Lee JS
影响因子：
64.5
作者：
Balsalobre, A;Damiola, F;Schibler, U
通讯作者：
Schibler, U
影响因子：
13.9
作者：
Mohawk JA;Green CB;Takahashi JS
通讯作者：
Takahashi JS
影响因子：
64.8
作者：
Nielsen, SJ;Schneider, R;Kouzarides, T
通讯作者：
Kouzarides, T
影响因子：
56.9
作者：
Godinho, Sofia I. H.;Maywood, Elizabeth S.;Nolan, Patrick M.
通讯作者：
Nolan, Patrick M.