Splicing enhances recruitment of methyltransferase HYPB/Setd2 and methylation of histone H3 Lys36
Splicing enhances recruitment of methyltransferase HYPB/Setd2 and methylation of histone H3 Lys36
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DOI：
10.1038/nsmb.2123
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发表时间：
2011-09-01
影响因子：
16.8
通讯作者：
Carmo-Fonseca, Maria
中科院分区：
文献类型：
--
作者：
de Almeida, Sergio Fernandes;Grosso, Ana Rita;Carmo-Fonseca, Maria
最近的一些证据支持染色质在剪接调控中的作用。在这里，我们表明，剪接也可以有助于组蛋白修饰，这意味着表观遗传机制和RNA加工之间的双向通信。人类细胞系和小鼠原代T细胞中组蛋白甲基化的全基因组分析揭示，相对于无内含子基因，含内含子基因优先标记有组蛋白H3 Lys 36三甲基化（H3 K36 me 3）。在含内含子的基因中，H3 K36 me 3标记与转录活性成比例，而在无内含子的基因中，H3 K36 me 3总是以低得多的水平检测到。此外，剪接抑制损害H3 K36甲基转移酶HYPB（也称为Setd 2）的募集并减少H3 K36 me 3，而剪接激活具有相反的效果。此外，H3 K36 me 3的增加与第一内含子的长度相关，这与剪接增强H3甲基化的观点一致。我们建议，剪接是机械耦合到招聘HYPB/Setd 2延长RNA聚合酶II。
Several lines of recent evidence support a role for chromatin in splicing regulation. Here, we show that splicing can also contribute to histone modification, which implies bidirectional communication between epigenetic mechanisms and RNA processing. Genome-wide analysis of histone methylation in human cell lines and mouse primary T cells reveals that intron-containing genes are preferentially marked with histone H3 Lys36 trimethylation (H3K36me3) relative to intronless genes. In intron-containing genes, H3K36me3 marking is proportional to transcriptional activity, whereas in intronless genes, H3K36me3 is always detected at much lower levels. Furthermore, splicing inhibition impairs recruitment of H3K36 methyltransferase HYPB (also known as Setd2) and reduces H3K36me3, whereas splicing activation has the opposite effect. Moreover, the increase of H3K36me3 correlates with the length of the first intron, consistent with the view that splicing enhances H3 methylation. We propose that splicing is mechanistically coupled to recruitment of HYPB/Setd2 to elongating RNA polymerase II.