Four putative SWI2/SNF2 chromatin remodelers have dual roles in regulating DNA methylation in Arabidopsis

First author: Dong-Lei Yang; Affiliations: Shanghai Center for Plant Stress Biology and Center of Excellence in Molecular Plant Sciences (中科院上海植物逆境生物学研究中心和分子植物科学卓越创新中心): Shanghai, China

Corresponding author: Jian-Kang Zhu (朱健康)

DNA methylation is a conserved epigenetic mark that is critical for many biological processes in plants and mammals. In Arabidopsis, the antagonistic activities (拮抗活性) of RNA-directed DNA methylation (RdDM) and ROS1-dependent active DNA demethylation are key for the dynamic regulation of locus-specific DNA methylation. However, the molecular factors that coordinate RdDM and active demethylation are largely unknown. Here we report that CLSY4 and its three paralogous SWI2/SNF2-type chromatin-remodeling proteins function in both RdDM and DNA demethylation in Arabidopsis. We initially identified CLSY4 in a genetic screen for DNA demethylation factors and subsequently demonstrated that it also is important in RdDM. Comprehensive genetic analyses using single and high order mutants of CLSY family proteins revealed their roles as double agents in the balance between methylation and demethylation reactions. The four CLSY proteins collectively are necessary for the canonical (权威的) RdDM pathway; at the same time, each CLSY likely mediates DNA demethylation at specific loci where DNA methylation depends on RdDM. These results indicate that the four chromatin-remodeling proteins have dual functions in regulating genomic DNA methylation, and thus provide new insights into the dynamic regulation of DNA methylation in a model multicellular eukaryotic organism.

DNA甲基化是一类十分保守的表观标记，其在动植物的许多生物学过程中均发挥重要作用。在拟南芥中，RNA指导的DNA甲基化RdDM和ROS1介导的DNA去甲基化之间的拮抗活性对于位点特异性DNA甲基化的动态调控至关重要。然而，生物体内协调RdDM和DNA去甲基化之间的分子机制还不清楚。本文报道了CLSY4蛋白及其四个旁系同源SWI2/SNF2类染色质重塑蛋白在拟南芥的RdDM和DNA去甲基化中发挥重要作用。作者首先在遗传筛查中鉴定了CLSY4作为DNA去甲基化因子，并在随后的试验中证明了其同时在RdDM也发挥重要功能。通过利用CLSY家族的单突或者高阶突变，作者发现这些基因在甲基化和去甲基化的平衡中发挥着双向作用。四个CLSY蛋白均作用于经典的RdDM通路，同时每一个CLSY蛋白似乎又在依赖于RdDM的DNA甲基化位点上介导DNA去甲基化。本文的研究结果揭示了四个染色质重塑蛋白在调控基因组DNA甲基化过程中具有双重作用，该研究为模式多细胞的真核生物中有关DNA甲基化的动态调控研究提供了新的视野。

通讯：朱健康（http://sourcedb.sibs.cas.cn/zw/rck/201206/t20120615_3598633.html）

个人简介：1983-1987年，北京农业大学，土壤农业化学学士；1987-1990年，加州大学河滨分校，植物学硕士；1990-1993年，普度大学，植物生理学博士；1994年，洛克菲勒大学，分子生物学博士后。

研究方向：渗透胁迫的感应和信号传导；低温胁迫的感应和信号传导；耐盐和耐氧化的机制；RNA介导的DNA甲基化；DNA去甲基化及其调控。

doi: https://doi.org/10.1038/s41421-018-0056-8

Journal: Cell Discovery

Published date: 16 October, 2018

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