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Mol Cell. 2014 Aug 7;55(3):495-504. doi: 10.1016/j.molcel.2014.06.009. Epub 2014 Jul 10.

Mechanism of DNA methylation-directed histone methylation by KRYPTONITE.

Author information

1
Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
2
Department of Molecular, Cell and Developmental Biology, University of California at Los Angeles, Los Angeles, CA 90095, USA.
3
Howard Hughes Medical Institute, University of California at Los Angeles, Los Angeles, CA 90095, USA.
4
Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California at Los Angeles, Los Angeles, CA 90095, USA.
5
Department of Biological Chemistry, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
#
Contributed equally

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.

PMID:
25018018
PMCID:
PMC4127122
DOI:
10.1016/j.molcel.2014.06.009
[Indexed for MEDLINE]
Free PMC Article

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