| Literature DB >> 25263594 |
Rui Guo1, Lijuan Zheng1, Juw Won Park2, Ruitu Lv1, Hao Chen1, Fangfang Jiao1, Wenqi Xu1, Shirong Mu3, Hong Wen4, Jinsong Qiu5, Zhentian Wang1, Pengyuan Yang1, Feizhen Wu1, Jingyi Hui3, Xiangdong Fu5, Xiaobing Shi4, Yujiang Geno Shi6, Yi Xing7, Fei Lan8, Yang Shi9.
Abstract
BS69 (also called 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 sequencing shows that BS69 mainly regulates intron retention (IR), which is the least 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 that BS69 connects histone H3.3K36me3 to regulated RNA splicing, providing significant, important insights into chromatin regulation of pre-mRNA processing.Entities:
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Year: 2014 PMID： 25263594 PMCID： PMC4363072 DOI： 10.1016/j.molcel.2014.08.022
Source DB: PubMed Journal: Mol Cell ISSN： 1097-2765 Impact factor: 17.970