Li Deng#, Guangfeng Zhu#, Wenying Zhong#, Zhibo Jia#, Qiangwei Zhou, Minyan Zhang, Zhixin Si, Qing Zhang, Yafeng Liang, Xuan Du, Yanfei Mao, Jian Wu, Guoliang Li, Jinxiong Shen, Jian-Kang Zhu*, Lun Zhao*

Nature Plants, Published: 02 April 2026

Abstract

DNA demethylation is essential for maintaining genome-wide DNA methylation balance. Despite the substantial risk to genome stability, the prevailing paradigm posits that the Arabidopsis demethylase ROS1 prevents genome-wide DNA hypermethylation in vivo mainly through its 5-methylcytosine DNA glycosylase/lyase activity. Here we challenge this paradigm by demonstrating that ROS1, through its occupancy, drives extensive passive demethylation independent of its glycosylase/lyase activity and maintains hypomethylation primarily by preventing de novo DNA methylation. This occupancy-based mechanism eliminates the need for genome-wide base excision for active demethylation, thereby minimizing threats to genomic fidelity and stability. Beyond its role in demethylation, ROS1 also functions as a key marker and regulator of chromatin accessibility. This regulation operates in both DNA methylation-dependent and -independent contexts, with ROS1 acting as either a reserve or active protector of accessible chromatin, depending on the functional state of DNA methylation systems. Our findings redefine the diverse roles of ROS1 in DNA methylation regulation and chromatin accessibility, highlighting their intricate interplay.

论文链接：https://www.nature.com/articles/s41477-026-02258-z