Genome-wide phosphoacetylation of histone H3 at Drosophila enhancers and promoters.

Genome-wide phosphoacetylation of histone H3 at Drosophila enhancers and promoters.
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DOI:
10.1101/gr.136929.111
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发表时间:
2012-06
期刊:
影响因子:
7
通讯作者:
Corces VG
Corces VG
中科院分区:
生物学1区
文献类型:
--
作者:
Kellner WA;Ramos E;Van Bortle K;Takenaka N;Corces VG

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转录调节由结合序列特异性转录因子的增强子介导,所述序列特异性转录因子又与它们控制的基因的启动子相互作用。在这里,我们表明,JIL-1激酶存在于蜕皮激素诱导的果蝇基因的增强子和启动子,在那里它磷酸化组蛋白H3的Ser 10和Ser 28残基。JIL-1也是CREB结合蛋白(CBP)介导的Lys 27乙酰化所必需的,Lys 27是活性增强子的良好表征标记。这些蛋白质在蜕皮激素诱导基因的增强子和启动子处的存在导致在两个调节序列处建立H3 K9 acS 10 ph和H3 K27 acS 28 ph标记。这些修饰对于14-3-3的募集是必要的,14 -3-3是一种能够促进两个同时结合的蛋白质之间相互作用的支架蛋白。染色质构象捕获分析表明,增强子和启动子之间的相互作用依赖于JIL-1,14-3-3,和CBP的存在。全基因组分析将这些结论扩展到大多数果蝇基因,表明JIL-1,H3 K9 acS 10 ph和H3 K27 acS 28 ph的存在是这种生物体中增强子和启动子的一般特征。
Transcription regulation is mediated by enhancers that bind sequence-specific transcription factors, which in turn interact with the promoters of the genes they control. Here, we show that the JIL-1 kinase is present at both enhancers and promoters of ecdysone-induced Drosophila genes, where it phosphorylates the Ser10 and Ser28 residues of histone H3. JIL-1 is also required for CREB binding protein (CBP)-mediated acetylation of Lys27, a well-characterized mark of active enhancers. The presence of these proteins at enhancers and promoters of ecdysone-induced genes results in the establishment of the H3K9acS10ph and H3K27acS28ph marks at both regulatory sequences. These modifications are necessary for the recruitment of 14-3-3, a scaffolding protein capable of facilitating interactions between two simultaneously bound proteins. Chromatin conformation capture assays indicate that interaction between the enhancer and the promoter is dependent on the presence of JIL-1, 14-3-3, and CBP. Genome-wide analyses extend these conclusions to most Drosophila genes, showing that the presence of JIL-1, H3K9acS10ph, and H3K27acS28ph is a general feature of enhancers and promoters in this organism.
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