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Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription

Nature Genetics volume 19, pages 187–191 (1998)Cite this article

Abstract

CpG methylation in vertebrates correlates with alterations in chromatin structure and gene silencing1,2,3,4. Differences in DNA-methylation status are associated with imprinting phenomena and carcinogenesis5,6,7,8,9,10. In Xenopus laevis oocytes, DNA methylation dominantly silences transcription through the assembly of a repressive nucleosomal array5. Methylated DNA assembled into chromatin binds the transcriptional repressor MeCP2 which cofractionates with Sin3 and histone deacetylase. Silencing conferred by MeCP2 and methylated DNA can be relieved by inhibition of histone deacetylase, facilitating the remodelling of chromatin and transcriptional activation. These results establish a direct causal relationship between DNA methylation-dependent transcriptional silencing and the modification of chromatin.

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Figure 1: Cofractionation of a histone deacetylase with MeCP2 and Sin3.
Figure 2: MeCP2, Sin3 and histone-deacetylase activity coimmunopricipitate.
Figure 3: Properties of Xenopus MeCP2. a, Sequence comparison of Xenopus MeCP2 (xMeCP2), rat MeCP2 (rMeCP2) and human MeCP2 (hMeCP2) proteins.
Figure 4: The MRD effectively represses transcription in frog oocytes in a TSA-sensitive manner.

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Acknowledgements

P.L.J. was funded by a Pharmacology Research Associate Program fellowship (NIH, NIGMS). G.C.V. was funded by the Netherlands Org. Sci. Research.

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Authors and Affiliations

  1. Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, National Institute of Health, Bethesda, 20892-5431, Maryland, USA

    Peter L. Jones, Gert Jan C. Veenstra, Paul A. Wade, Danielle Vermaak, John Strouboulis & Alan P. Wolffe

  2. Department of Experimental Molecular Biology, Janssen Research Foundation, Turnboutseweg 30, 2340, Bearse, Belgium

    Stefan U. Kass

  3. Dipartimento Biologia Strutturale e Funzionale, Universita di Varese, V. Ravasi 2, 2100, Varese, Italy

    Nicoletta Landsberger

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Correspondence to Alan P. Wolffe.

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Jones, P., Veenstra, G., Wade, P. et al. Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription . Nat Genet 19, 187–191 (1998). https://doi.org/10.1038/561

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