Interactions with RNA direct the Polycomb group protein SCML2 to chromatin where it represses target genes.
Interactions with RNA direct the Polycomb group protein SCML2 to chromatin where it represses target genes.
复制标题
DOI：
10.7554/elife.02637
复制
发表时间：
2014-07-01
期刊：
影响因子：
7.7
通讯作者：
Reinberg D
中科院分区：
文献类型：
--
作者：
Bonasio R;Lecona E;Narendra V;Voigt P;Parisi F;Kluger Y;Reinberg D
Polycomb 抑制复合物-1 (PRC1) 对于基因表达的表观遗传调控至关重要。 SCML2 是果蝇 SCM 的哺乳动物同源物，果蝇 SCM 是一种与 PRC1 相关的多梳族蛋白。在这项研究中，我们表明 SCML2A（一种与染色质紧密相关的 SCML2 亚型）有助于 PRC1 定位，并且还直接强制抑制某些 Polycomb 靶基因。 SCML2A 通过其 SPM 结构域与 PRC1 结合，并通过新型 RNA 结合区 (RBR) 与 ncRNA 相互作用。 SCML2A 靶向染色质涉及 MBT 结构域的协调作用、RNA 结合以及通过 SPM 结构域与 PRC1 的相互作用。 RBR 的缺失会减少 SCML2A 在靶基因上的占据，而缺乏 RBR 的突变体 SCML2A 的过度表达会导致 PRC1 募集缺陷。这些观察结果指出了 ncRNA 在调节 SCML2 功能中的作用，并表明 SCML2 直接并与 PRC1 合作参与转录的表观遗传控制。 DOI：http://dx.doi.org/10.7554/eLife.02637.001 我们体内几乎每个细胞都具有相同的基因，但在任何时候，不同的细胞都会打开不同的基因。细胞中的大部分 DNA 包裹在称为组蛋白的蛋白质周围，形成称为染色质的紧凑结构。染色质中的 DNA 通常非常紧密，以至于无法访问或打开 DNA 中的基因。一种名为 Polycomb Repressive Complex 1（或简称 PRC1）的蛋白质复合物将 DNA 包装到染色质中，以关闭（并阻止）植物和动物中的基因。已知其他蛋白质与该复合物的结合较弱，包括果蝇中一种称为 SCM 的蛋白质。然而，这种蛋白质尚未得到广泛研究。博纳西奥、莱科纳等人。现在已经研究了这种与人类染色质结合的蛋白质的相关版本。这些实验表明，这种称为 SCML2A 的蛋白质也与 RNA 分子结合，Bonasio、Lecona 等人。还发现了 SCML2A 中一个以前未被识别的结构域，该结构域与这些分子相互作用。与该蛋白中与 PRC1 和组蛋白结合的其他结构域一样，SCML2A 需要其 RNA 结合区域能够与染色质结合，以便靶向并关闭某些基因。因此，博纳西奥、莱科纳等人的研究结果。支持 RNA 分子可以调节基因表达的模型，并表明一些 RNA 分子通过与 SCML2A 相互作用来做到这一点。未来的工作需要解决 RNA 分子是否作为指导将 SCML2A 引导至需要关闭的特定基因，或者这些分子的作用是否更复杂。 DOI：http://dx.doi.org/10.7554/eLife.02637.002
Polycomb repressive complex-1 (PRC1) is essential for the epigenetic regulation of gene expression. SCML2 is a mammalian homolog of Drosophila SCM, a Polycomb-group protein that associates with PRC1. In this study, we show that SCML2A, an SCML2 isoform tightly associated to chromatin, contributes to PRC1 localization and also directly enforces repression of certain Polycomb target genes. SCML2A binds to PRC1 via its SPM domain and interacts with ncRNAs through a novel RNA-binding region (RBR). Targeting of SCML2A to chromatin involves the coordinated action of the MBT domains, RNA binding, and interaction with PRC1 through the SPM domain. Deletion of the RBR reduces the occupancy of SCML2A at target genes and overexpression of a mutant SCML2A lacking the RBR causes defects in PRC1 recruitment. These observations point to a role for ncRNAs in regulating SCML2 function and suggest that SCML2 participates in the epigenetic control of transcription directly and in cooperation with PRC1. DOI: http://dx.doi.org/10.7554/eLife.02637.001 Almost every cell in our bodies has the same genes but at any one time different genes will be switched on in different cells. Much of the DNA in a cell is wrapped around proteins called histones to form a compact structure called chromatin. The DNA in chromatin is often so tightly packed that the genes in the DNA cannot to be accessed or switched on. A complex of proteins called the Polycomb Repressive Complex 1 (or PRC1 for short) pack DNA into chromatin to switch genes off (and keep them off) in both plants and animals. Other proteins are known to weakly bind to this complex, including one called SCM in fruit flies. However, this protein has not been extensively studied. Bonasio, Lecona et al. have now looked at a related version of this protein that binds to chromatin in humans. These experiments revealed that this protein, which is called SCML2A, also binds to molecules of RNA, and Bonasio, Lecona et al. also identified a previously unrecognized domain within SCML2A that interacts with these molecules. Like other domains in this protein that bind to PRC1 and histones, SCML2A needs its RNA-binding region to be able to bind to chromatin in order to target and switch off certain genes. As such, the findings of Bonasio, Lecona et al. support models whereby RNA molecules can regulate the expression of genes, and suggest that some RNA molecules do this by interacting with SCML2A. Future work is needed to address whether RNA molecules serve as guides that direct SCML2A to specific genes that need to be switched off, or whether these molecules' roles are more complex. DOI: http://dx.doi.org/10.7554/eLife.02637.002