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

First author: Ming Zhou; Affiliations: Salk Institute for Biological Studies (萨克生物研究所): La Jolla, USA

Corresponding author: Julie A. Law

DNA methylation is essential for gene regulation, transposon silencing (转座子沉默) and imprinting (印记). 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 (染色质重塑因子), CLASSY (CLSY) 1–4, are required for both locus-specific and global regulation of DNA methylation in Arabidopsis thaliana. 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 (相似的) pathways may operate in a broad range of organisms.

DNA甲基化对于基因调控、转座沉默及基因印记都十分重要。尽管特异DNA甲基化模式的产生对于这些进程非常重要，然而在每个位点上甲基化是如何被调控的还不清楚。本文报道了拟南芥中四个染色质重塑因子CLASSY1-4对于位点特异性的以及整体的DNA甲基化调控至关重要。这些因子与RNA聚合酶IV一起控制24个核苷酸小干扰RNA（24nt-siRNA）的产生，而这些siRNA作用于指导DNA甲基化。CLSYs调控Pol-IV与染色质的关联以及数千个独立位点上24nt-siRNA的产生，进而一起调控几乎所有的24nt-siRNA。由于CLSYs的参与，这个调控过程依赖于不同抑制的染色质修饰来促进位点特异性的DNA甲基化控制。考虑到植物和哺乳动物之间甲基化系统的保守性，作者认为本文所发现的甲基化调控机制可能适合更加广泛的物种。

通讯：Julie A. Law (https://www.salk.edu/scientist/julie-law/)

研究方向：利用模式植物拟南芥研究表观修饰。

doi: 10.1038/s41588-018-0115-y

Journal: Nature Genetics

Published online: 07 May, 2018

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