A DNA adenine demethylase impairs PRC2-mediated repression of genes marked by a specific chromatin signature

Genome Biology

Research

Xuan Ma¹  Jingjing Tian¹  Yu Zhao¹  Shicheng Gong¹  Xinran Zhang¹  Qian Liu¹  Bo Zhu¹  Qingxiao Jia¹  Junjie Li¹  Wentao Wang¹  Meng Yuan¹  Sheng Li¹  Dao-Xiu Zhou² 

[1] National Key Laboratory of Crop Genetic Improvement, Hubei Hongshan Laboratory, Huazhong Agricultural University, 430070, Wuhan, China;National Key Laboratory of Crop Genetic Improvement, Hubei Hongshan Laboratory, Huazhong Agricultural University, 430070, Wuhan, China;Institute of Plant Science Paris-Saclay (IPS2), CNRS, INRAE, University Paris-Saclay, 91405, Orsay, France;

关键词: ALKBH1;    DNA adenine methylation (6mA);    R-loop;    H3K27me3;    Polycomb repressive complex 2 (PRC2);   

DOI  :  10.1186/s13059-023-03042-4

 received in 2023-02-16, accepted in 2023-08-21,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundThe Fe (II)- and α-ketoglutarate-dependent AlkB family dioxygenases are implicated in nucleotide demethylation. AlkB homolog1 (ALKBH1) is shown to demethylate DNA adenine methylation (6mA) preferentially from single-stranded or unpaired DNA, while its demethylase activity and function in the chromatin context are unclear.ResultsHere, we find that loss-of-function of the rice ALKBH1 gene leads to increased 6mA in the R-loop regions of the genome but has a limited effect on the overall 6mA level. However, in the context of mixed tissues, rather than on individual loci, the ALKBH1 mutation or overexpression mainly affects the expression of genes with a specific combination of chromatin modifications in the body region marked with H3K4me3 and H3K27me3 but depleted of DNA CG methylation. In the similar context of mixed tissues, further analysis reveals that the ALKBH1 protein preferentially binds to genes marked by the chromatin signature and has a function to maintain a high H3K4me3/H3K27me3 ratio by impairing the binding of Polycomb repressive complex 2 (PRC2) to the targets, which is required for both the basal and stress-induced expression of the genes.ConclusionOur findings unravel a function of ALKBH1 to control the balance between the antagonistic histone methylations for gene activity and provide insight into the regulatory mechanism of PRC2-mediated H3K27me3 deposition within the gene body region.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

【 图 表 】

Fig. 3

Fig. 1

Fig. 2

Fig. 1

Figs. 1

Fig. 7

12888_2023_5124_Article_IEq1.gif

Fig. 7

Fig. 5

Fig. 6

Fig. 5

Fig. 1

Fig. 1