Substrate deformation regulates DRM2-mediated DNA methylation in plants

Fang，Jian1; Leichter，Sarah M.2,3; Jiang，Jianjun2,3; Biswal，Mahamaya1; Lu，Jiuwei1; Zhang，Zhi Min1; Ren，Wendan1; Zhai，Jixian4; Cui，Qiang5; Zhong，Xuehua2,3; Song，Jikui1,6

2021-06-01

10.1126/sciadv.abd9224

Science Advances   影响因子和分区

2375-2548

DNA methylation is a major epigenetic mechanism critical for gene expression and genome stability. In plants, domains rearranged methyltransferase 2 (DRM2) preferentially mediates CHH (H = C, T, or A) methylation, a substrate specificity distinct from that of mammalian DNA methyltransferases. However, the underlying mechanism is unknown. Here, we report structure-function characterization of DRM2-mediated methylation. An arginine finger from the catalytic loop intercalates into the nontarget strand of DNA through the minor groove, inducing large DNA deformation that affects the substrate preference of DRM2. The target recognition domain stabilizes the enlarged major groove via shape complementarity rather than base-specific interactions, permitting substrate diversity. The engineered DRM2 C397R mutation introduces base-specific contacts with the +2-flanking guanine, thereby shifting the substrate specificity of DRM2 toward CHG DNA. Together, this study uncovers DNA deformation as a mechanism in regulating the specificity of DRM2 toward diverse CHH substrates and illustrates methylome complexity in plants.

SCI ; EI

英语

NI期刊

其他

WOS:000658757100004

20212310466684

Alkylation ; Amino acids ; Deformation ; Gene expression ; Mammals ; Methylation ; Substrates

Biological Materials and Tissue Engineering:461.2 ; Biology:461.9 ; Chemical Reactions:802.2 ; Chemical Operations:802.3 ; Organic Compounds:804.1

2-s2.0-85107291860

Scopus

1.Department of Biochemistry,University of California,Riverside,Riverside,92521,United States
2.Laboratory of Genetics,University of Wisconsin-Madison,Madison,53706,United States
3.Wisconsin Institute for Discovery,University of Wisconsin-Madison,Madison,53715,United States
4.Department of Biology,Institute of Plant and Food Science,Southern University of Science and Technology,Shenzhen, Guangdong,518055,China
5.Departments of Chemistry,Physics,and Biomedical Engineering,Boston University,Boston,02215,United States
6.Environmental Toxicology Graduate Program,University of California,Riverside,Riverside,92521,United States

Fang，Jian,Leichter，Sarah M.,Jiang，Jianjun,et al. Substrate deformation regulates DRM2-mediated DNA methylation in plants[J]. Science Advances,2021,7(23).

Fang，Jian.,Leichter，Sarah M..,Jiang，Jianjun.,Biswal，Mahamaya.,Lu，Jiuwei.,...&Song，Jikui.(2021).Substrate deformation regulates DRM2-mediated DNA methylation in plants.Science Advances,7(23).

Fang，Jian,et al."Substrate deformation regulates DRM2-mediated DNA methylation in plants".Science Advances 7.23(2021).