dREAM co-operates with insulator-binding proteins and regulates expression at divergently paired genes.

dREAM co-operates with insulator-binding proteins and regulates expression at divergently paired genes.
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DOI:
10.1093/nar/gku609
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发表时间:
2014-08
影响因子:
14.9
通讯作者:
Dyson NJ
Dyson NJ
中科院分区:
生物学2区
文献类型:
--
作者:
Korenjak M;Kwon E;Morris RT;Anderssen E;Amzallag A;Ramaswamy S;Dyson NJ

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dREAM复合物代表果蝇中E2 F/RBF阻遏物复合物的主要形式。dREAM与果蝇基因组中的数千个位点相关,但其作用机制尚不清楚。为了了解dREAM作用的基因组背景,我们研究了果蝇E2 F和dREAM蛋白的分布和定位。在这里,我们报告了一个惊人的和意想不到的重叠dE 2F 2/dREAM网站和结合位点的绝缘体结合蛋白CP 190和Beaf-32。遗传分析表明,这些组件的功能合作和染色质免疫沉淀实验的突变动物证明,dE 2F 2是重要的协会的CP 190与染色质。dE 2F 2/dREAM结合位点在趋异转录的基因处富集,并且大多数通过dE 2F 2耗尽上调的基因代表差异表达的趋异转录的基因对的被抑制的一半。突变动物的分析证实,dREAM和CP 190同样需要在这些基因对的转录完整性,并建议,dREAM的功能与CP 190的音乐会,以建立抑制/激活基因之间的界限。与dREAM与绝缘子结合蛋白协同作用的想法一致,由dREAM结合的基因组区域具有依赖于多个dREAM组分的增强子阻断活性。这些发现表明dREAM在转录结构域的组织中起作用。
dREAM complexes represent the predominant form of E2F/RBF repressor complexes in Drosophila. dREAM associates with thousands of sites in the fly genome but its mechanism of action is unknown. To understand the genomic context in which dREAM acts we examined the distribution and localization of Drosophila E2F and dREAM proteins. Here we report a striking and unexpected overlap between dE2F2/dREAM sites and binding sites for the insulator-binding proteins CP190 and Beaf-32. Genetic assays show that these components functionally co-operate and chromatin immunoprecipitation experiments on mutant animals demonstrate that dE2F2 is important for association of CP190 with chromatin. dE2F2/dREAM binding sites are enriched at divergently transcribed genes, and the majority of genes upregulated by dE2F2 depletion represent the repressed half of a differentially expressed, divergently transcribed pair of genes. Analysis of mutant animals confirms that dREAM and CP190 are similarly required for transcriptional integrity at these gene pairs and suggest that dREAM functions in concert with CP190 to establish boundaries between repressed/activated genes. Consistent with the idea that dREAM co-operates with insulator-binding proteins, genomic regions bound by dREAM possess enhancer-blocking activity that depends on multiple dREAM components. These findings suggest that dREAM functions in the organization of transcriptional domains.
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