title: Mechanism of DNA methylation-directed histone methylation by KRYPTONITE.
abstract: In Arabidopsis, CHG DNA methylation is controlled by the H3K9 methylation mark through a self-reinforcing loop between DNA methyltransferase CHROMOMETHYLASE3 (CMT3) and H3K9 histone methyltransferase KRYPTONITE/SUVH4 (KYP). We report on the structure of KYP in complex with methylated DNA, substrate H3 peptide, and cofactor SAH, thereby defining the spatial positioning of the SRA domain relative to the SET domain. The methylated DNA is bound by the SRA domain with the 5mC flipped out of the DNA, while the H3(1-15) peptide substrate binds between the SET and post-SET domains, with the ε-ammonium of K9 positioned adjacent to bound SAH. These structural insights, complemented by functional data on key mutants of residues lining the 5mC and H3K9-binding pockets within KYP, establish how methylated DNA recruits KYP to the histone substrate. Together, the structures of KYP and previously reported CMT3 complexes provide insights into molecular mechanisms linking DNA and histone methylation.
authors.affiliation: Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Jiamu
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Lianna M
authors.initials: LM
authors.lastname: Johnson
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California at Los Angeles, Los Angeles, CA 90095, USA.|Howard Hughes Medical Institute, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Groth
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California at Los Angeles, Los Angeles, CA 90095, USA.|Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California at Los Angeles, Los Angeles, CA 90095, USA.|Howard Hughes Medical Institute, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Suhua
authors.initials: S
authors.lastname: Feng
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Hale
authors.affiliation: Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Sisi
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Biological Chemistry, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Ajay A
authors.initials: AA
authors.lastname: Vashisht
authors.affiliation: Department of Biological Chemistry, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Wohlschlegel
authors.affiliation: Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Dinshaw J
authors.initials: DJ
authors.lastname: Patel
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California at Los Angeles, Los Angeles, CA 90095, USA.|Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California at Los Angeles, Los Angeles, CA 90095, USA.|Howard Hughes Medical Institute, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Jacobsen
mesh_terms: D017360:Arabidopsis / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D029681:Arabidopsis Proteins / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites / Q000235:genetics; D019175:DNA Methylation; D018744:DNA, Plant / Q000737:chemistry* / Q000235:genetics*; D044127:Epigenesis, Genetic; D018506:Gene Expression Regulation, Plant; D018745:Genome, Plant; D011495:Histone-Lysine N-Methyltransferase / Q000737:chemistry* / Q000378:metabolism*; D006657:Histones / Q000502:physiology*; D008958:Models, Molecular; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D014961:X-Ray Diffraction
chemical_list: D029681:Arabidopsis Proteins; D018744:DNA, Plant; D006657:Histones; D012435:S-Adenosylhomocysteine; D011495:Histone-Lysine N-Methyltransferase; C471228:SUVH4 protein, Arabidopsis