Positive cofactor 4 (PC4) contributes to the regulation of replication-dependent canonical histone gene expression

IF 2.946 Q3 Biochemistry, Genetics and Molecular Biology BMC Molecular Biology Pub Date : 2018-07-27 DOI:10.1186/s12867-018-0110-y
Aleksandra Brzek, Marlena Cichocka, Jakub Dolata, Wojciech Juzwa, Daniel Schümperli, Katarzyna Dorota Raczynska
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引用次数: 3

Abstract

Core canonical histones are required in the S phase of the cell cycle to pack newly synthetized DNA, therefore the expression of their genes is highly activated during DNA replication. In mammalian cells, this increment is achieved by both enhanced transcription and 3′ end processing. In this paper, we described positive cofactor 4 (PC4) as a protein that contributes to the regulation of replication-dependent histone gene expression.

We showed that PC4 influences RNA polymerase II recruitment to histone gene loci in a cell cycle-dependent manner. The most important effect was observed in S phase where PC4 knockdown leads to the elevated level of RNA polymerase II on histone genes, which corresponds to the increased total level of those gene transcripts. The opposite effect was caused by PC4 overexpression. Moreover, we found that PC4 has a negative effect on the unique 3′ end processing of histone pre-mRNAs that can be based on the interaction of PC4 with U7 snRNP and CstF64. Interestingly, this effect does not depend on the cell cycle.

We conclude that PC4 might repress RNA polymerase II recruitment and transcription of replication-dependent histone genes in order to maintain the very delicate balance between histone gene expression and DNA synthesis. It guards the cell from excess of histones in S phase. Moreover, PC4 might promote the interaction of cleavage and polyadenylation complex with histone pre-mRNAs, that might impede with the recruitment of histone cleavage complex. This in turn decreases the 3′ end processing efficiency of histone gene transcripts.

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正辅因子4 (PC4)参与了复制依赖性典型组蛋白基因表达的调控
核心规范组蛋白在细胞周期的S期需要包装新合成的DNA,因此其基因的表达在DNA复制期间被高度激活。在哺乳动物细胞中,这种增加是通过增强的转录和3 '端加工来实现的。在本文中,我们将正辅因子4 (PC4)描述为一种有助于调节复制依赖性组蛋白基因表达的蛋白质。我们发现PC4以细胞周期依赖的方式影响RNA聚合酶II向组蛋白基因位点的募集。最重要的影响是在S期观察到的,PC4敲低导致组蛋白基因上RNA聚合酶II水平升高,这与这些基因转录物的总水平增加相对应。PC4过表达则产生相反的效果。此外,我们发现PC4对组蛋白前mrna独特的3 '端加工具有负面影响,这可能是基于PC4与U7 snRNP和CstF64的相互作用。有趣的是,这种效果并不依赖于细胞周期。我们得出结论,PC4可能抑制RNA聚合酶II的募集和复制依赖性组蛋白基因的转录,以维持组蛋白基因表达和DNA合成之间的微妙平衡。它在S期保护细胞免受过量组蛋白的侵害。此外,PC4可能促进裂解和聚腺苷化复合体与组蛋白前mrna的相互作用,从而阻碍组蛋白裂解复合体的募集。这反过来又降低了组蛋白基因转录本的3 '端加工效率。
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来源期刊
BMC Molecular Biology
BMC Molecular Biology 生物-生化与分子生物学
CiteScore
4.80
自引率
0.00%
发文量
0
审稿时长
>12 weeks
期刊介绍: BMC Molecular Biology is an open access journal publishing original peer-reviewed research articles in all aspects of DNA and RNA in a cellular context, encompassing investigations of chromatin, replication, recombination, mutation, repair, transcription, translation and RNA processing and function.
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