Position-specific intron retention is mediated by the histone methyltransferase SDG725.
Position-specific intron retention is mediated by the histone methyltransferase SDG725.
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位置特异性内含子保留由组蛋白甲基转移酶 SDG725 介导。
DOI：
10.1186/s12915-018-0513-8
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发表时间：
2018-04-30
期刊：
影响因子：
5.4
通讯作者：
Ni T
中科院分区：
文献类型：
--
作者：
Wei G;Liu K;Shen T;Shi J;Liu B;Han M;Peng M;Fu H;Song Y;Zhu J;Dong A;Ni T
内含子保留（IR）是植物中最常见的选择性剪接形式，在植物发育和逆境胁迫反应中对基因表达起着重要作用。然而，IR调节的分子机制仍然很大程度上未知。SDG 725是水稻中的组蛋白H3赖氨酸36（H3 K36）特异性甲基转移酶，其敲低导致超过4700个基因的IR改变。令人惊讶的是，在SDG 725敲低突变体中，IR事件在5′区域整体增加，但在3′区域减少。染色质免疫沉淀测序分析显示，SDG 725缺失导致H3 K36单甲基化（H3 K36 me 1）的全基因组增加，但出乎意料的是，H3 K36二甲基化和三甲基化（H3 K36 me 2和H3 K36 me 3）的启动子近端移位。与动物中的结果一致，水稻中H3 K36 me 1/me 2/me 3的水平与基因表达水平正相关，而H3 K36 me 2/me 3的移位与IR的位置特异性改变一致。我们发现H3 K36 me 2或H3 K36 me 3单独有助于SDG 725敲除引起的IR位置变化，尽管当H3 K36 me 2和H3 K36 me 3修饰同时移位时IR移位更显著。我们的结果表明，SDG 725以位置特异性方式调节IR，这表明H3 K36甲基化在RNA剪接中发挥作用，可能是通过标记植物中保留的内含子。本文的在线版本（10.1186/s12915-018-0513-8）包含补充材料，可供授权用户使用。
Intron retention (IR), the most prevalent alternative splicing form in plants, plays a critical role in gene expression during plant development and stress response. However, the molecular mechanisms underlying IR regulation remain largely unknown. Knockdown of SDG725, a histone H3 lysine 36 (H3K36)-specific methyltransferase in rice, leads to alterations of IR in more than 4700 genes. Surprisingly, IR events are globally increased at the 5′ region but decreased at the 3′ region of the gene body in the SDG725-knockdown mutant. Chromatin immunoprecipitation sequencing analyses reveal that SDG725 depletion results in a genome-wide increase of the H3K36 mono-methylation (H3K36me1) but, unexpectedly, promoter-proximal shifts of H3K36 di- and tri-methylation (H3K36me2 and H3K36me3). Consistent with the results in animals, the levels of H3K36me1/me2/me3 in rice positively correlate with gene expression levels, whereas shifts of H3K36me2/me3 coincide with position-specific alterations of IR. We find that either H3K36me2 or H3K36me3 alone contributes to the positional change of IR caused by SDG725 knockdown, although IR shift is more significant when both H3K36me2 and H3K36me3 modifications are simultaneously shifted. Our results revealed that SDG725 modulates IR in a position-specific manner, indicating that H3K36 methylation plays a role in RNA splicing, probably by marking the retained introns in plants. The online version of this article (10.1186/s12915-018-0513-8) contains supplementary material, which is available to authorized users.
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