BS69/ZMYND11 reads and connects histone H3.3 lysine 36 trimethylation-decorated chromatin to regulated pre-mRNA processing.
BS69/ZMYND11 reads and connects histone H3.3 lysine 36 trimethylation-decorated chromatin to regulated pre-mRNA processing.
复制标题
DOI：
10.1016/j.molcel.2014.08.022
复制
发表时间：
2014-10-23
期刊：
影响因子：
16
通讯作者：
Shi, Yang
中科院分区：
文献类型：
--
作者：
Guo, Rui;Zheng, Lijuan;Park, Juw Won;Lv, Ruitu;Chen, Hao;Jiao, Fangfang;Xu, Wenqi;Mu, Shirong;Wen, Hong;Qiu, Jinsong;Wang, Zhentian;Yang, Pengyuan;Wu, Feizhen;Hui, Jingyi;Fu, Xiangdong;Shi, Xiaobing;Shi, Yujiang Geno;Xing, Yi;Lan, Fei;Shi, Yang
BS 69（aka ZMYND 11）含有串联排列的PHD、BROMO和PWWP结构域，它们是染色质识别模式。在这里，我们表明，BS 69选择性识别组蛋白变体H3.3赖氨酸36三甲基化（H3.3K36me3）通过其染色质结合域。我们进一步鉴定了BS 69与RNA剪接调节因子的关联，包括剪接体的U 5 snRNP组分，如EFTUD 2。值得注意的是，RNA-seq显示BS 69主要调节内含子保留（IR），这是哺乳动物细胞中最不了解的RNA选择性剪接事件。生化和遗传实验表明，BS 69通过物理相互作用拮抗EFTUD 2促进IR。我们进一步表明，IR的调节BS 69也依赖于其结合H3 K36 me 3修饰的染色质。总而言之，我们的研究确定了H3.3K36me3特异性阅读器和IR调节因子，并揭示了BS 69在将组蛋白H3.3K36me3连接到受调节的RNA剪接方面的新颖且意想不到的作用，为染色质调节前体mRNA加工提供了重要的新见解。
BS69 (aka ZMYND11) contains tandemly arranged PHD, BROMO and PWWP domains, which are chromatin recognition modalities. Here we show that BS69 selectively recognizes histone variant H3.3 lysine 36 trimethylation (H3.3K36me3) via its chromatin-binding domains. We further identify BS69 association with RNA splicing regulators including the U5 snRNP components of the spliceosome such as EFTUD2. Remarkably, RNA-seq shows that BS69 mainly regulates intron retention (IR), which is the least well-understood RNA alternative splicing event in mammalian cells. Biochemical and genetic experiments demonstrate that BS69 promotes IR by antagonizing EFTUD2 through physical interactions. We further show that regulation of IR by BS69 also depends on its binding to H3K36me3-decorated chromatin. Taken together, our study identifies an H3.3K36me3-specific reader and a regulator of IR, and reveals a novel and unexpected role of BS69 in connecting histone H3.3K36me3 to regulated RNA splicing, providing significant new insights into chromatin regulation of pre-mRNA processing.
登录
查看更多内容
影响因子：
64.5
作者：
Goldberg AD;Banaszynski LA;Noh KM;Lewis PW;Elsaesser SJ;Stadler S;Dewell S;Law M;Guo X;Li X;Wen D;Chapgier A;DeKelver RC;Miller JC;Lee YL;Boydston EA;Holmes MC;Gregory PD;Greally JM;Rafii S;Yang C;Scambler PJ;Garrick D;Gibbons RJ;Higgs DR;Cristea IM;Urnov FD;Zheng D;Allis CD
通讯作者：
Allis CD
影响因子：
5.3
作者：
Dittmar, Kimberly A.;Jiang, Peng;Carstens, Russell P.
通讯作者：
Carstens, Russell P.
影响因子：
10.5
作者：
Munding, Elizabeth M.;Igel, A. Haller;Ares, Manuel, Jr.
通讯作者：
Ares, Manuel, Jr.
影响因子：
30.8
作者：
Kolasinska-Zwierz P;Down T;Latorre I;Liu T;Liu XS;Ahringer J
通讯作者：
Ahringer J
影响因子：
64.5
作者：
Braunschweig U;Gueroussov S;Plocik AM;Graveley BR;Blencowe BJ
通讯作者：
Blencowe BJ