TY - JOUR
T1 - Molecular mechanism of action of plant DRM de novo DNA methyltransferases
AU - Zhong, Xuehua
AU - Du, Jiamu
AU - Hale, Christopher J.
AU - Gallego-Bartolome, Javier
AU - Feng, Suhua
AU - Vashisht, Ajay A.
AU - Chory, Joanne
AU - Wohlschlegel, James A.
AU - Patel, Dinshaw J.
AU - Jacobsen, Steven E.
N1 - Funding Information:
We thank the staff members at Shanghai Synchrotron Radiation Facility (SSRF) and Advanced Photon Source for their support in diffraction data collection and the staff members at the UCLA BSCRC BioSequencing core for high-throughput sequencing. We are grateful to Craig Pikaard for discussions on strand-biased DNA methylation, Dr. Jianping Ding for access to data collection at the SSRF, and Dr. Eerappa Rajakumara for assistance with cloning. X.Z. is a research fellow of Ruth L. Kirschstein National Research Service Award (F32GM096483-01). C.J.H. is a HHMI fellow of the Damon Runyon Cancer Research Foundation. S.F. is a special fellow of the Leukemia & Lymphoma Society. J.G-B is a Human Frontiers Science Program fellow (LT000425/2012-L). This work was supported by the Abby Rockefeller Mauze Trust and Maloris and STARR foundations (to D.J.P.), NIH grant GM089778 and the UCLA Jonsson Cancer Center (to J.A.W.), NIH grant GM60398 (to S.E.J.), and NIH grant GM094428 (to J.C.). S.E.J. and J.C. are investigators of the Howard Hughes Medical Institute.
PY - 2014/5/22
Y1 - 2014/5/22
N2 - DNA methylation is a conserved epigenetic gene-regulation mechanism. DOMAINS REARRANGED METHYLTRANSFERASE (DRM) is a key de novo methyltransferase in plants, but how DRM acts mechanistically is poorly understood. Here, we report the crystal structure of the methyltransferase domain of tobacco DRM (NtDRM) and reveal a molecular basis for its rearranged structure. NtDRM forms a functional homodimer critical for catalytic activity. We also show that Arabidopsis DRM2 exists in complex with the small interfering RNA (siRNA) effector ARGONAUTE4 (AGO4) and preferentially methylates one DNA strand, likely the strand acting as the template for RNA polymerase V-mediated noncoding RNA transcripts. This strand-biased DNA methylation is also positively correlated with strand-biased siRNA accumulation. These data suggest a model in which DRM2 is guided to target loci by AGO4-siRNA and involves base-pairing of associated siRNAs with nascent RNA transcripts.
AB - DNA methylation is a conserved epigenetic gene-regulation mechanism. DOMAINS REARRANGED METHYLTRANSFERASE (DRM) is a key de novo methyltransferase in plants, but how DRM acts mechanistically is poorly understood. Here, we report the crystal structure of the methyltransferase domain of tobacco DRM (NtDRM) and reveal a molecular basis for its rearranged structure. NtDRM forms a functional homodimer critical for catalytic activity. We also show that Arabidopsis DRM2 exists in complex with the small interfering RNA (siRNA) effector ARGONAUTE4 (AGO4) and preferentially methylates one DNA strand, likely the strand acting as the template for RNA polymerase V-mediated noncoding RNA transcripts. This strand-biased DNA methylation is also positively correlated with strand-biased siRNA accumulation. These data suggest a model in which DRM2 is guided to target loci by AGO4-siRNA and involves base-pairing of associated siRNAs with nascent RNA transcripts.
UR - http://www.scopus.com/inward/record.url?scp=84901379529&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2014.03.056
DO - 10.1016/j.cell.2014.03.056
M3 - Article
C2 - 24855943
AN - SCOPUS:84901379529
SN - 0092-8674
VL - 157
SP - 1050
EP - 1060
JO - Cell
JF - Cell
IS - 5
ER -