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Rbm10 facilitates heterochromatin assembly via the Clr6 HDAC complex
Epigenetics & Chromatin ( IF 3.9 ) Pub Date : 2021-01-19 , DOI: 10.1186/s13072-021-00382-y
Martina Weigt 1 , Qingsong Gao 1 , Hyoju Ban 2 , Haijin He 2 , Guido Mastrobuoni 3 , Stefan Kempa 3 , Wei Chen 1, 4, 5 , Fei Li 2
Affiliation  

Splicing factors have recently been shown to be involved in heterochromatin formation, but their role in controlling heterochromatin structure and function remains poorly understood. In this study, we identified a fission yeast homologue of human splicing factor RBM10, which has been linked to TARP syndrome. Overexpression of Rbm10 in fission yeast leads to strong global intron retention. Rbm10 also interacts with splicing factors in a pattern resembling that of human RBM10, suggesting that the function of Rbm10 as a splicing regulator is conserved. Surprisingly, our deep-sequencing data showed that deletion of Rbm10 caused only minor effect on genome-wide gene expression and splicing. However, the mutant displays severe heterochromatin defects. Further analyses indicated that the heterochromatin defects in the mutant did not result from mis-splicing of heterochromatin factors. Our proteomic data revealed that Rbm10 associates with the histone deacetylase Clr6 complex and chromatin remodelers known to be important for heterochromatin silencing. Deletion of Rbm10 results in significant reduction of Clr6 in heterochromatin. Our work together with previous findings further suggests that different splicing subunits may play distinct roles in heterochromatin regulation.

中文翻译:

Rbm10 通过 Clr6 HDAC 复合物促进异染色质组装

剪接因子最近被证明与异染色质形成有关,但它们在控制异染色质结构和功能中的作用仍然知之甚少。在这项研究中,我们鉴定了人类剪接因子 RBM10 的裂殖酵母同源物,它与 TARP 综合征有关。Rbm10 在裂变酵母中的过表达导致强烈的全局内含子保留。Rbm10 还与剪接因子以类似于人类 RBM10 的模式相互作用,这表明 Rbm10 作为剪接调节剂的功能是保守的。令人惊讶的是,我们的深度测序数据显示 Rbm10 的缺失对全基因组基因表达和剪接仅造成轻微影响。然而,突变体显示出严重的异染色质缺陷。进一步的分析表明,突变体中的异染色质缺陷不是由异染色质因子的错误拼接引起的。我们的蛋白质组学数据显示,Rbm10 与组蛋白去乙酰化酶 Clr6 复合物和已知对异染色质沉默很重要的染色质重塑剂相关。Rbm10 的缺失导致异染色质中 Clr6 的显着减少。我们与之前的研究结果一起进一步表明,不同的剪接亚基可能在异染色质调控中发挥不同的作用。
更新日期:2021-01-20
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