A Nucleosome Bridging Mechanism for Activation of a Maintenance DNA Methyltransferase

Caitlin I Stoddard; Suhua Feng; Melody G Campbell; Wanlu Liu; Haifeng Wang; Xuehua Zhong; Yana Bernatavichute; Yifan Cheng; Steven E Jacobsen; Geeta J Narlikar

doi:10.1016/j.molcel.2018.10.006

A Nucleosome Bridging Mechanism for Activation of a Maintenance DNA Methyltransferase

Mol Cell. 2019 Jan 3;73(1):73-83.e6. doi: 10.1016/j.molcel.2018.10.006. Epub 2018 Nov 8.

Authors

Affiliations

¹ Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA; Tetrad Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.
² Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edyth Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA.
³ Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
⁴ Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁵ Basic Forestry and Proteomics Research Center, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, China; Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁶ Laboratory of Genetics & Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53715, USA.
⁷ Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁸ Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
⁹ Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edyth Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: jacobsen@ucla.edu.
¹⁰ Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: geeta.narlikar@ucsf.edu.

Abstract

DNA methylation and H3K9me are hallmarks of heterochromatin in plants and mammals, and are successfully maintained across generations. The biochemical and structural basis for this maintenance is poorly understood. The maintenance DNA methyltransferase from Zea mays, ZMET2, recognizes dimethylation of H3K9 via a chromodomain (CD) and a bromo adjacent homology (BAH) domain, which flank the catalytic domain. Here, we show that dinucleosomes are the preferred ZMET2 substrate, with DNA methylation preferentially targeted to linker DNA. Electron microscopy shows one ZMET2 molecule bridging two nucleosomes within a dinucleosome. We find that the CD stabilizes binding, whereas the BAH domain enables allosteric activation by the H3K9me mark. ZMET2 further couples recognition of H3K9me to an increase in the specificity for hemimethylated versus unmethylated DNA. We propose a model in which synergistic coupling between recognition of nucleosome spacing, H3K9 methylation, and DNA modification allows ZMET2 to maintain DNA methylation in heterochromatin with high fidelity.

Keywords: DNA methylation; H3K9me; chromatin; heterochromatin; maize; nucleosome; plants.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
DNA Methylation*
DNA Modification Methylases / genetics
DNA Modification Methylases / metabolism*
DNA Modification Methylases / ultrastructure
Enzyme Activation
Escherichia coli / enzymology
Escherichia coli / genetics
Microscopy, Electron
Models, Molecular
Nucleic Acid Conformation
Nucleosomes / chemistry
Nucleosomes / enzymology*
Nucleosomes / genetics
Nucleosomes / ultrastructure
Plant Proteins / genetics
Plant Proteins / metabolism*
Plant Proteins / ultrastructure
Protein Binding
Protein Interaction Domains and Motifs
Structure-Activity Relationship
Substrate Specificity
Xenopus laevis / genetics
Xenopus laevis / metabolism

Substances

Nucleosomes
Plant Proteins
DNA Modification Methylases
ZMET2 protein, Zea mays

Abstract

Publication types

MeSH terms

Substances

Grants and funding