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首页> 外文期刊>Journal of Bioinformatics and Computational Biology >Histone modifications influence skipped exons inclusion
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Histone modifications influence skipped exons inclusion

机译：组蛋白修饰影响跳过的外显子包含

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摘要

Alternative splicing (AS), by which individual genes can produce multiple mRNA, associates with genomic complexity, disease, and development. Histone modifications show important roles in both transcription initiation and mRNA splicing. Here, we intended to find the link between AS and histone modifications in flanking regions through analyzing publicly available data in two human cell lines, GM12878 and K562 cell lines. According to exon inclusion levels, exons were classified into three types, included skipped exons, excluded skipped exons and expressed constitutive exons. We revealed that the inclusion levels of skipped exons (SEs) were negatively correlated with the enrichment of active histone marks in SEs, indicating a role of histone modifications in AS. We also found that active histone modifications were enriched in the upstream exons of SEs, especially around 50 splicing sites. We inferred that the histone modifications around the 50 splicing sites in upstream exon of the SEs could help RNA Polymerase II complex to recruit the effector proteins and facilitate AS. It was indicated that nucleosome occupancy had little influence on the inclusion levels of SEs. At last, we proposed an integrated model that describe how histone modifications affected the pre- mRNA splicing.
机译：选择性剪接 （AS） 是单个基因可以产生多个 mRNA 的产物，它与基因组复杂性、疾病和发育有关。组蛋白修饰在转录起始和 mRNA 剪接中都显示出重要作用。在这里，我们打算通过分析两种人类细胞系（GM12878 和 K562 细胞系）中的公开数据来找到侧翼区域 AS 和组蛋白修饰之间的联系。根据外显子包涵水平，将外显子分为3种类型，包括跳过的外显子、排除的跳过的外显子和表达的组成型外显子。我们发现，跳过的外显子（SEs）的包含水平与SEs中活性组蛋白标记的富集呈负相关，表明组蛋白修饰在AS中的作用。我们还发现，活性组蛋白修饰富集在SEs的上游外显子中，尤其是50个左右的剪接位点。我们推断，SEs上游外显子中50个剪接位点周围的组蛋白修饰可以帮助RNA聚合酶II复合物募集效应蛋白并促进AS。结果表明，核小体占有率对SEs的包涵水平影响不大。最后，我们提出了一个描述组蛋白修饰如何影响前mRNA剪接的集成模型。

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