CG10543蛋白参与调控蜕皮激素依赖基因的转录

IF 2.5 1区 数学 Q1 MATHEMATICS
N. E. Vorobyova, Iu. V. Nikolenko, A. N. Krasnov
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引用次数: 0

摘要

摘要尽管关于复制起始点特性的数据越来越多,但基因组中起始点识别复合体(ORC)定位的分子机制仍然知之甚少。研究表明,决定ORC在基因组中定位的关键因素是DNA结合蛋白,这些DNA结合蛋白形成了各种DNA调控元件,包括绝缘子、启动子和增强子,从而将复制程序与不同水平的转录调控联系起来。在此之前,我们证明了Su(Hw)蛋白是这种蛋白的第一个例子。随后的研究发现了包括CG10543在内的许多其他dna结合蛋白,它们可能负责形成相应的调控元件,并将转录和复制复合物募集到其结合位点。研究表明,果蝇CG10543蛋白与SAGA复合物的去泛素化(DUB)模块相互作用。CG10543蛋白的结合位点主要位于活性基因的启动子区域,并与SAGA和dSWI/SNF染色质修饰和重塑复合体以及ORC复制复合体共定位。为了研究CG10543蛋白在转录调控中的作用,我们在正常条件下和RNA干扰CG10543蛋白的情况下,在果蝇S2细胞中进行了RNA- seq实验。结果表明,CG10543蛋白影响469个基因的转录,其中相当一部分(23%)是蜕皮激素依赖基因。蜕皮激素是果蝇体内主要的类固醇激素,负责果蝇的变态,在发育过程中对许多基因的表达有重要影响。我们发现CG10543位点与具有活性调控元件特征的CBP蛋白和组蛋白标记H3K27Ac共定位。CG10543蛋白也与CP190蛋白共定位,提示通过调控元件之间形成远程相互作用的潜在转录调控机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
CG10543 Protein Is Involved in the Regulation of Transcription of Ecdysone-Dependent Genes

Abstract

Despite increasing data on the properties of the origins of replication, the molecular mechanisms underlying the origin recognition complex (ORC) positioning in the genome are still poorly understood. It has been suggested that the key factors determining the positioning of ORC in the genome are DNA-binding proteins that form various DNA regulatory elements, including insulators, promoters, and enhancers, thereby linking the replication program to different levels of transcriptional regulation. Previously, we demonstrated that the Su(Hw) protein is the first example of such a protein. Subsequent studies identified a number of other DNA-binding proteins, including CG10543, which may be responsible for the formation of the corresponding regulatory elements and the recruitment of transcriptional and replication complexes to their binding sites. It has been shown that the Drosophila CG10543 protein interacts with the deubiquitinating (DUB) module of the SAGA complex. The binding sites of the CG10543 protein are predominantly located in the promoter regions of active genes and colocalize with the SAGA and dSWI/SNF chromatin modification and remodeling complexes, as well as with the ORC replication complex. To investigate the role of the CG10543 protein in transcriptional regulation, an RNA-Seq experiment was conducted in Drosophila S2 cells under normal conditions and upon RNA interference with the CG10543 protein. It was shown that the CG10543 protein affects the transcription of 469 genes, with a significant portion of these genes (23%) being ecdysone-dependent genes. Ecdysone is the main steroid hormone in Drosophila, is responsible for Drosophila metamorphosis, and has a significant effect on the expression of many genes during development. We demonstrated that CG10543 sites colocalize with the CBP protein and the histone mark H3K27Ac, which are characteristic of active regulatory elements. The CG10543 protein also colocalizes with the CP190 protein, suggesting a potential mechanism of transcriptional regulation through the formation of long-range interactions between regulatory elements.

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来源期刊
CiteScore
3.70
自引率
4.50%
发文量
34
审稿时长
6-12 weeks
期刊介绍: Geometric And Functional Analysis (GAFA) publishes original research papers of the highest quality on a broad range of mathematical topics related to geometry and analysis. GAFA scored in Scopus as best journal in "Geometry and Topology" since 2014 and as best journal in "Analysis" since 2016. Publishes major results on topics in geometry and analysis. Features papers which make connections between relevant fields and their applications to other areas.
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