Histone H1.5 binds over splice sites in chromatin and regulates alternative splicing
Histone H1.5 binds over splice sites in chromatin and regulates alternative splicing
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DOI：
10.1093/nar/gkz338
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发表时间：
2019-07-09
影响因子：
14.9
通讯作者：
Ast, Gil
中科院分区：
文献类型：
--
作者：
Glaich, Ohad;Leader, Yodfat;Ast, Gil
染色质组织和表观遗传标记影响剪接，虽然这些影响的大小和机制在很大程度上是未知的。在这里，我们证明，连接组蛋白H1.5影响mRNA剪接。我们观察到，接头组蛋白H1.5结合DNA的剪接位点的短外显子在人肺成纤维细胞（IMR90细胞）。我们发现H1.5与这些剪接位点的关联与包含选择性剪接外显子的水平相关。由H1.5标记的外显子在3 '剪接位点附近比不与H1.5相关的外显子具有更多的RNA聚合酶II（RNAP II）停滞。在细胞耗尽的H1.5，我们表明，包括五个外显子评估减少，RNAP II水平在这些外显子也减少。我们的研究结果表明，H1.5参与剪接位点选择和选择性剪接的调节，以前没有证明连接组蛋白的功能。
Chromatin organization and epigenetic markers influence splicing, though the magnitudes of these effects and the mechanisms are largely unknown. Here, we demonstrate that linker histone H1.5 influences mRNA splicing. We observed that linker histone H1.5 binds DNA over splice sites of short exons in human lung fibroblasts (IMR90 cells). We found that association of H1.5 with these splice sites correlated with the level of inclusion of alternatively spliced exons. Exons marked by H1.5 had more RNA polymerase II (RNAP II) stalling near the 3 ' splice site than did exons not associated with H1.5. In cells depleted of H1.5, we showed that the inclusion of five exons evaluated decreased and that RNAP II levels over these exons were also reduced. Our findings indicate that H1.5 is involved in regulation of splice site selection and alternative splicing, a function not previously demonstrated for linker histones.