TY - JOUR
T1 - Mechanistic basis for maintenance of CHG DNA methylation in plants
AU - Fang, Jian
AU - Jiang, Jianjun
AU - Leichter, Sarah M.
AU - Liu, Jie
AU - Biswal, Mahamaya
AU - Khudaverdyan, Nelli
AU - Zhong, Xuehua
AU - Song, Jikui
N1 - Funding Information:
We thank staff members at the NE-CAT beamlines (GM124165), Advanced Photo Source (DE-AC02-06CH11357), Argonne National Laboratory for access to X-ray beamline. We thank Dr. Hak Soo Seo for providing a bacterial expression plasmid for CMT3 for in vitro enzymatic analysis. This work was supported by NIH grant (R35GM119721) to J.S, University of California Cancer Research Coordinating Committee (UC CRCC) grant (CRR-20-634140) to J.S., NIH (1R35GM124806), and NSF CAREER (1552455) to X.Z. S.M.L. is supported by NIH T32 (GM008349).
Funding Information:
We thank staff members at the NE-CAT beamlines (GM124165), Advanced Photo Source (DE-AC02-06CH11357), Argonne National Laboratory for access to X-ray beamline. We thank Dr. Hak Soo Seo for providing a bacterial expression plasmid for CMT3 for in vitro enzymatic analysis. This work was supported by NIH grant (R35GM119721) to J.S, University of California Cancer Research Coordinating Committee (UC CRCC) grant (CRR-20-634140) to J.S., NIH (1R35GM124806), and NSF CAREER (1552455) to X.Z. S.M.L. is supported by NIH T32 (GM008349).
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - DNA methylation is an evolutionarily conserved epigenetic mechanism essential for transposon silencing and heterochromatin assembly. In plants, DNA methylation widely occurs in the CG, CHG, and CHH (H = A, C, or T) contexts, with the maintenance of CHG methylation mediated by CMT3 chromomethylase. However, how CMT3 interacts with the chromatin environment for faithful maintenance of CHG methylation is unclear. Here we report structure-function characterization of the H3K9me2-directed maintenance of CHG methylation by CMT3 and its Zea mays ortholog ZMET2. Base-specific interactions and DNA deformation coordinately underpin the substrate specificity of CMT3 and ZMET2, while a bivalent readout of H3K9me2 and H3K18 allosterically stimulates substrate binding. Disruption of the interaction with DNA or H3K9me2/H3K18 led to loss of CMT3/ZMET2 activity in vitro and impairment of genome-wide CHG methylation in vivo. Together, our study uncovers how the intricate interplay of CMT3, repressive histone marks, and DNA sequence mediates heterochromatic CHG methylation.
AB - DNA methylation is an evolutionarily conserved epigenetic mechanism essential for transposon silencing and heterochromatin assembly. In plants, DNA methylation widely occurs in the CG, CHG, and CHH (H = A, C, or T) contexts, with the maintenance of CHG methylation mediated by CMT3 chromomethylase. However, how CMT3 interacts with the chromatin environment for faithful maintenance of CHG methylation is unclear. Here we report structure-function characterization of the H3K9me2-directed maintenance of CHG methylation by CMT3 and its Zea mays ortholog ZMET2. Base-specific interactions and DNA deformation coordinately underpin the substrate specificity of CMT3 and ZMET2, while a bivalent readout of H3K9me2 and H3K18 allosterically stimulates substrate binding. Disruption of the interaction with DNA or H3K9me2/H3K18 led to loss of CMT3/ZMET2 activity in vitro and impairment of genome-wide CHG methylation in vivo. Together, our study uncovers how the intricate interplay of CMT3, repressive histone marks, and DNA sequence mediates heterochromatic CHG methylation.
UR - http://www.scopus.com/inward/record.url?scp=85133438707&partnerID=8YFLogxK
U2 - 10.1038/s41467-022-31627-3
DO - 10.1038/s41467-022-31627-3
M3 - Article
C2 - 35790763
AN - SCOPUS:85133438707
SN - 2041-1723
VL - 13
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 3877
ER -