Promoter-like epigenetic signatures in exons displaying cell type-specific splicing.
Promoter-like epigenetic signatures in exons displaying cell type-specific splicing.
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DOI：
10.1186/s13059-015-0797-8
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发表时间：
2015-10-23
期刊：
影响因子：
12.3
通讯作者：
Guigó R
中科院分区：
文献类型：
--
作者：
Curado J;Iannone C;Tilgner H;Valcárcel J;Guigó R
前体mRNA剪接主要以共转录方式发生，核小体密度和组蛋白修饰都被认为在剪接位点识别和调节中起作用。然而，这种相互作用背后的程度和机制仍然知之甚少。我们使用ENCODE项目产生的转录组和表观基因组数据来研究染色质结构和选择性剪接之间的关联。我们发现H3 K9 ac，H3 K27 ac，H3 K4 me 3，活性启动子的表观遗传标记特征和外显子包含在一个小但定义明确的外显子类别中（约占所有受调控外显子的4%）之间存在强烈且显著的正相关。这些外显子在细胞类型中系统地维持在相对低的包含水平，但是当物理上接近活性启动子时，它们的包含在特定细胞类型中显著增强。组蛋白修饰和激活转录的其他染色质特征可以被增选以参与物理上接近启动子区域的外显子的剪接的调节。本文的在线版本（doi：10.1186/s13059-015-0797-8）包含补充材料，可供授权用户使用。
Pre-mRNA splicing occurs mainly co-transcriptionally, and both nucleosome density and histone modifications have been proposed to play a role in splice site recognition and regulation. However, the extent and mechanisms behind this interplay remain poorly understood. We use transcriptomic and epigenomic data generated by the ENCODE project to investigate the association between chromatin structure and alternative splicing. We find a strong and significant positive association between H3K9ac, H3K27ac, H3K4me3, epigenetic marks characteristic of active promoters, and exon inclusion in a small but well-defined class of exons, representing approximately 4 % of all regulated exons. These exons are systematically maintained at comparatively low levels of inclusion across cell types, but their inclusion is significantly enhanced in particular cell types when in physical proximity to active promoters. Histone modifications and other chromatin features that activate transcription can be co-opted to participate in the regulation of the splicing of exons that are in physical proximity to promoter regions. The online version of this article (doi:10.1186/s13059-015-0797-8) contains supplementary material, which is available to authorized users.