Molecular characterization of Mybbp1a as a co-repressor on the Period2 promoter.
Molecular characterization of Mybbp1a as a co-repressor on the Period2 promoter.
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DOI：
10.1093/nar/gkn1013
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发表时间：
2009-03
影响因子：
14.9
通讯作者：
Ishida N
中科院分区：
文献类型：
--
作者：
Hara Y;Onishi Y;Oishi K;Miyazaki K;Fukamizu A;Ishida N
生物钟由时钟基因的转录反馈环组成。隐花色素是哺乳动物负反馈环的重要组成部分，因为它们抑制了Clock-BMAL1介导的转录。我们从肉瘤180细胞中纯化了小鼠CRY1(MCRY1)蛋白复合体，以确定它们在昼夜基因表达中的作用，并发现Myb结合蛋白1a(Mybp1a)与mCRY1相互作用。Mybbp1a调节多种转录因子，但其在昼夜节律基因表达中的作用尚不清楚。在报告实验中，我们发现Mybbp1a是PER2表达的辅助抑制因子，并抑制了PER2启动子的活性。染色质免疫沉淀(ChIP)分析显示，内源性Mybbp1a与PER2启动子结合，与mCRY1的结合在时间上匹配。此外，Mybbp1a与PER2启动子的结合与PER2表达下调的开始相关，也与组蛋白H3 Lys9的二甲基化有关，它也可以与组蛋白H3 Lys9结合。这些发现表明，Mybbp1a和mCRY1可以在PER2启动子上形成复合体，作为PER2表达的负调控因子。
The circadian clock comprises transcriptional feedback loops of clock genes. Cryptochromes are essential components of the negative feedback loop in mammals as they inhibit CLOCK-BMAL1-mediated transcription. We purified mouse CRY1 (mCRY1) protein complexes from Sarcoma 180 cells to determine their roles in circadian gene expression and discovered that Myb-binding protein 1a (Mybbp1a) interacts with mCRY1. Mybbp1a regulates various transcription factors, but its role in circadian gene expression is unknown. We found that Mybbp1a functions as a co-repressor of Per2 expression and repressed Per2 promoter activity in reporter assays. Chromatin immunoprecipitation (ChIP) assays revealed endogenous Mybbp1a binding to the Per2 promoter that temporally matched that of mCRY1. Furthermore, Mybbp1a binding to the Per2 promoter correlated with the start of the down-regulation of Per2 expression and with the dimethylation of histone H3 Lys9, to which it could also bind. These findings suggest that Mybbp1a and mCRY1 can form complexes on the Per2 promoter that function as negative regulators of Per2 expression.
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影响因子：
64.5
作者：
Balsalobre, A;Damiola, F;Schibler, U
通讯作者：
Schibler, U
影响因子：
4.8
作者：
Nakayama, Manabu;Iida, Midori;Ohara, Osamu
通讯作者：
Ohara, Osamu
DOI：
10.1073/pnas.94.11.5831
发表时间：
1997-05-27
影响因子：
11.1
作者：
Mushegian, AR;Bassett, DE;Koonin, EV
通讯作者：
Koonin, EV
影响因子：
5.3
作者：
Chaves, I;Yagita, K;Tamanini, F
通讯作者：
Tamanini, F
影响因子：
4.8
作者：
Eggert, M;Michel, J;Renkawitz, R
通讯作者：
Renkawitz, R