ZNFX-1 Functions within Perinuclear Nuage to Balance Epigenetic Signals.

ZNFX-1 Functions within Perinuclear Nuage to Balance Epigenetic Signals.
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ZnFX-1在核周内的功能,以平衡表观遗传信号。

DOI:
10.1016/j.molcel.2018.04.009
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发表时间:
2018-05-17
期刊:
影响因子:
16
通讯作者:
Mello CC
Mello CC
中科院分区:
生物学1区
文献类型:
--
作者:
Ishidate T;Ozturk AR;Durning DJ;Sharma R;Shen EZ;Chen H;Seth M;Shirayama M;Mello CC

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动物细胞具有采用持久和可遗传的基因表达程序或表观遗传状态的显著能力,这些表观遗传状态定义了体细胞类型的物理特性和多样性。表观遗传程序的维持依赖于人们知之甚少的防止遗传信号获得或丢失的途径。在种系中,表观遗传因子富集在称为nuage的液体状核周浓缩物中。在这里,我们确定了高度保守的解旋酶结构域蛋白,ZNFX-1,作为一种表观遗传调节因子和nuage的组成部分,与Argonaute系统相互作用,以平衡表观遗传。我们的研究结果表明,ZNFX-1促进了3′端的募集机制,该机制传播了小RNA表观遗传信号,从而抵消了Argonaute靶向作用使mRNA沿着5′端移动的趋势。这些功能的见解支持的想法,最近确定的nuage亚结构域,包括ZNFX-1颗粒或“Z-颗粒”,可能会定义在表观遗传调控的分子活性的空间和时间区域。Ishidate等鉴定了ZNFX-1,一种高度保守的解旋酶蛋白,作为C.优雅的他们的研究结果表明,ZNFX-1定位于nuage内,在那里它与Argonaute系统和RNA依赖性RNA聚合酶(RdRP)相互作用,以确保小RNA信号沿着种系mRNA的平衡扩增。
Animal cells have a remarkable capacity to adopt durable and heritable gene expression programs or epigenetic states that define the physical properties and diversity of somatic cell types. The maintenance of epigenetic programs depends on poorly understood pathways that prevent gain or loss of inherited signals. In the germline, epigenetic factors are enriched in liquid-like perinuclear condensates called nuage. Here we identify the deeply conserved helicase-domain protein, ZNFX-1, as an epigenetic regulator and component of nuage that interacts with Argonaute systems to balance epigenetic inheritance. Our findings suggest that ZNFX-1 promotes the 3′ recruitment of machinery that propagates the small RNA epigenetic signal and thus counteracts a tendency for Argonaute-targeting to shift 5′ along the mRNA. These functional insights support the idea that recently identified subdomains of nuage, including ZNFX-1 granules or “Z-granules,” may define spatial and temporal zones of molecular activity during epigenetic regulation. Ishidate et al. identify ZNFX-1, a highly conserved helicase protein, as a factor required for epigenetic inheritance in C. elegans. Their findings indicate that ZNFX-1 localizes within nuage where it interacts with Argonaute systems and RNA-dependent RNA polymerase (RdRP) to ensure balanced amplification of small RNA signals along germline mRNAs.
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