Locus-specific control of the de novo DNA methylation pathway in Arabidopsis by the CLASSY family.

Locus-specific control of the de novo DNA methylation pathway in Arabidopsis by the CLASSY family.
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DOI:
10.1038/s41588-018-0115-y
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发表时间:
2018-06
期刊:
影响因子:
30.8
通讯作者:
Law JA
Law JA
中科院分区:
生物学1区
文献类型:
--
作者:
Zhou M;Palanca AMS;Law JA

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DNA甲基化对于基因调控、转座子沉默和印记是必不可少的。尽管特定DNA甲基化模式的产生对这些过程至关重要,但甲基化是如何在单个基因座上调节的仍不清楚。在这里,我们证明了一个由四个可能的染色质重塑因子组成的家族,Clasy(CLSY)1-4,对于拟南芥中DNA甲基化的位置特异性和全局调控都是必需的。从机制上讲,这些因子与RNA聚合酶-IV(Pol-IV)共同作用,控制引导DNA甲基化的24核苷酸小干扰RNA(24nt-siRNAs)的产生。CLsys单独地调节Pol-IV-染色质结合和数千个不同位点的24nt-siRNA的产生,它们共同调节基本上所有的24nt-siRNA。这种调节依赖于不同的抑制性染色质修饰来促进DNA甲基化的位点特异性控制,这取决于涉及的CLsys。鉴于植物和哺乳动物的甲基化系统之间的保守性,类似的途径可能在广泛的生物体中运作。
DNA methylation is essential for gene regulation, transposon silencing, and imprinting. Although the generation of specific DNA methylation patterns is critical for these processes, how methylation is regulated at individual loci remains unclear. Here we show that a family of four putative chromatin remodeling factors, CLASSY (CLSY) 1–4, are required for both locus-specific and global regulation of DNA methylation in Arabidopsis. Mechanistically, these factors act in connection with RNA polymerase-IV (Pol-IV) to control the production of 24-nucleotide small interfering RNAs (24nt-siRNAs), which guide DNA methylation. Individually, the CLSYs regulate Pol-IV-chromatin association and 24nt-siRNA production at thousands of distinct loci, and together, they regulate essentially all 24nt-siRNAs. Depending on the CLSYs involved, this regulation relies on different repressive chromatin modifications to facilitate locus-specific control of DNA methylation. Given the conservation between methylation systems in plants and mammals, analogous pathways likely operate in a broad range of organisms.
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