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Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex

Author

Listed:
  • Xinsheng Nan

    (Institute of Cell and Molecular Biology, University of Edinburgh)

  • Huck-Hui Ng

    (Institute of Cell and Molecular Biology, University of Edinburgh)

  • Colin A. Johnson

    (The Medical School, University of Birmingham)

  • Carol D. Laherty

    (Fred Hutchinson Cancer Research Center)

  • Bryan M. Turner

    (The Medical School, University of Birmingham)

  • Robert N. Eisenman

    (Fred Hutchinson Cancer Research Center)

  • Adrian Bird

    (Institute of Cell and Molecular Biology, University of Edinburgh)

Abstract

Cytosine residues in the sequence 5′CpG (cytosine–guanine) are often postsynthetically methylated in animal genomes. CpG methylation is involved in long-term silencing of certain genes during mammalian development1,2 and in repression of viral genomes3,4. The methyl-CpG-binding proteins MeCP1 (ref. 5) and MeCP2 (ref. 6) interact specifically with methylated DNA and mediate transcriptional repression7,8,9. Here we study the mechanism of repression by MeCP2, an abundant nuclear protein that is essential for mouse embryogenesis10. MeCP2 binds tightly to chromosomes in a methylation-dependent manner11,12. It contains a transcriptional-repression domain (TRD) that can function at a distance in vitro and in vivo9. We show that a region of MeCP2 that localizes with the TRD associates with a corepressor complex containing the transcriptional repressor mSin3A and histone deacetylases13,14,15,16,17,18,19. Transcriptional repression in vivo is relieved by the deacetylase inhibitor trichostatin A20, indicating that deacetylation of histones (and/or of other proteins) is an essential component of this repression mechanism. The data suggest that two global mechanisms of gene regulation, DNA methylation and histone deacetylation, can be linked by MeCP2.

Suggested Citation

  • Xinsheng Nan & Huck-Hui Ng & Colin A. Johnson & Carol D. Laherty & Bryan M. Turner & Robert N. Eisenman & Adrian Bird, 1998. "Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex," Nature, Nature, vol. 393(6683), pages 386-389, May.
    • Handle: RePEc:nat:nature:v:393:y:1998:i:6683:d:10.1038_30764
    DOI: 10.1038/30764
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    Cited by:

    1. Parker C. Wilson & Yoshiharu Muto & Haojia Wu & Anil Karihaloo & Sushrut S. Waikar & Benjamin D. Humphreys, 2022. "Multimodal single cell sequencing implicates chromatin accessibility and genetic background in diabetic kidney disease progression," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    2. Silvia Da Ros & Luca Aresu & Serena Ferraresso & Eleonora Zorzan & Eugenio Gaudio & Francesco Bertoni & Mauro Dacasto & Mery Giantin, 2018. "Validation of epigenetic mechanisms regulating gene expression in canine B-cell lymphoma: An in vitro and in vivo approach," PLOS ONE, Public Library of Science, vol. 13(12), pages 1-19, December.
    3. Boris Kantor & Bernadette O’Donovan & Joseph Rittiner & Dellila Hodgson & Nicholas Lindner & Sophia Guerrero & Wendy Dong & Austin Zhang & Ornit Chiba-Falek, 2024. "The therapeutic implications of all-in-one AAV-delivered epigenome-editing platform in neurodegenerative disorders," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    4. Patrick A Riley, 2018. "Epigenetic Error and Large-scale Genomic Instability in Cancer," Biomedical Journal of Scientific & Technical Research, Biomedical Research Network+, LLC, vol. 4(3), pages 3943-3946, May.

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