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.


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


  • Nucleosomes
  • Plant Proteins
  • DNA Modification Methylases
  • ZMET2 protein, Zea mays