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首页> 外文期刊>Epigenetics & Chromatin >Flightless-I governs cell fate by recruiting the SUMO isopeptidase SENP3 to distinct HOX genes
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Flightless-I governs cell fate by recruiting the SUMO isopeptidase SENP3 to distinct HOX genes

机译：Flightless-I通过将SUMO异肽酶SENP3募集到不同的HOX基因来控制细胞命运

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Background Despite recent studies on the role of ubiquitin-related SUMO modifier in cell fate decisions, our understanding on precise molecular mechanisms of these processes is limited. Previously, we established that the SUMO isopeptidase SENP3 regulates chromatin assembly of the MLL1/2 histone methyltransferase complex at distinct HOX genes, including the osteogenic master regulator DLX3 . A comprehensive mechanism that regulates SENP3 transcriptional function was not understood. Results Here, we identified flightless-I homolog (FLII), a member of the gelsolin family of actin-remodeling proteins, as a novel regulator of SENP3. We demonstrate that FLII is associated with SENP3 and the MLL1/2 complex. We further show that FLII determines SENP3 recruitment and MLL1/2 complex assembly on the DLX3 gene. Consequently, FLII is indispensible for H3K4 methylation and proper loading of active RNA polymerase II at this gene locus. Most importantly, FLII-mediated SENP3 regulation governs osteogenic differentiation of human mesenchymal stem cells. Conclusion Altogether, these data reveal a crucial functional interconnection of FLII with the sumoylation machinery that converges on epigenetic regulation and cell fate determination.
机译：背景技术尽管最近对泛素相关的SUMO修饰剂在细胞命运决定中的作用进行了研究，但我们对这些过程的精确分子机制的理解仍然有限。先前，我们建立了SUMO异肽酶SENP3调节MLL1 / 2组蛋白甲基转移酶复合物在不同HOX基因上的染色质组装，包括成骨主调节剂DLX3。尚不清楚调节SENP3转录功能的全面机制。结果在这里，我们鉴定了肌动蛋白重塑蛋白凝溶胶蛋白家族成员“ flying-I同源物”（FLII），作为SENP3的新型调节剂。我们证明FLII与SENP3和MLL1 / 2复合物相关。我们进一步表明，FLII在DLX3基因上确定SENP3募集和MLL1 / 2复合体装配。因此，FLII对于H3K4甲基化和在该基因位点正确加载活性RNA聚合酶II必不可少。最重要的是，FLII介导的SENP3调控支配人间充质干细胞的成骨分化。结论总而言之，这些数据揭示了FLII与融合在表观遗传调控和细胞命运确定上的SUMO化机制之间的关键功能互连。

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