Department of Biology, Emory University, Atlanta, Georgia 30322, USA.
Genome Res. 2012 Jun;22(6):1081-8. doi: 10.1101/gr.136929.111. Epub 2012 Apr 16.
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.
转录调控是通过结合序列特异性转录因子的增强子介导的，而转录因子反过来又与它们所调控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上，在那里它磷酸化组蛋白 H3 的 Ser10 和 Ser28 残基。JIL-1 还需要 CREB 结合蛋白 (CBP) 介导的 Lys27 乙酰化，Lys27 乙酰化是活性增强子的一个特征标记。这些蛋白质在蜕皮激素诱导的基因的增强子和启动子上的存在导致 H3K9acS10ph 和 H3K27acS28ph 标记在两个调节序列上的建立。这些修饰对于 14-3-3 的募集是必要的，14-3-3 是一种支架蛋白，能够促进同时结合的两个蛋白质之间的相互作用。染色质构象捕获分析表明，增强子与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、H3K9acS10ph 和 H3K27acS28ph 的存在是该生物体内增强子和启动子的一般特征。
