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A Nucleosome Bridging Mechanism for Activation of a Maintenance DNA Methyltransferase.
Stoddard, Caitlin I; Feng, Suhua; Campbell, Melody G; Liu, Wanlu; Wang, Haifeng; Zhong, Xuehua; Bernatavichute, Yana; Cheng, Yifan; Jacobsen, Steven E; Narlikar, Geeta J.
Afiliação
  • Stoddard CI; 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.
  • Feng S; 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.
  • Campbell MG; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Liu W; 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.
  • Wang H; 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.
  • Zhong X; Laboratory of Genetics & Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53715, USA.
  • Bernatavichute Y; Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Cheng Y; 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.
  • Jacobsen SE; 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,
  • Narlikar GJ; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: geeta.narlikar@ucsf.edu.
Mol Cell ; 73(1): 73-83.e6, 2019 01 03.
Article em En | MEDLINE | ID: mdl-30415948
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.
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Proteínas de Plantas / Nucleossomos / Metilases de Modificação do DNA / Metilação de DNA Limite: Animals Idioma: En Revista: Mol Cell Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Adicionar na Minha BVS
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XML
PubMed Links
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Proteínas de Plantas / Nucleossomos / Metilases de Modificação do DNA / Metilação de DNA Limite: Animals Idioma: En Revista: Mol Cell Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos