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Methyl CpG binding proteins: coupling chromatin architecture to gene regulation

Oncogene volume 20, pages 3166–3173 (2001)Cite this article

Abstract

A correlation between DNA methylation and transcriptional silencing has existed for many years. Recently, substantial progress has been reported in the search for proteins that interpret the regulatory information inherent in DNA methylation and translate this information into functional states, resulting in the identification of a family of highly conserved proteins, the MBD family. Direct connections between these proteins and histone modification enzymes have emerged as a common theme, implying that DNA methylation exerts its effects primarily through repressive chromatin architecture. Recent structural determinations of the DNA binding domain of two MBD family members, MeCP2 and MBD1, provide a framework to model the interactions of this family with DNA. Comparative sequence analysis and experimental DNA binding data can be interpreted using this structural framework allowing one to contrast the members of the MBD family with each other and to predict the properties of new family members. The identification of mutations in MeCP2, the founding member of this family, as causal for the neurological developmental disorder Rett Syndrome provides additional information regarding amino acid residues crucial to the functions of this interesting protein family.

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Acknowledgements

I thank Timur Yusufzai and Alan Wolffe for communication of results prior to publication. I thank Dr Paula Vertino and Dr Xiaodong Cheng for critical reading of this manuscript. Research in my laboratory is supported by grants from the National Institute of Child Health and Human Development (1 K22 HD01238-01) and from the Rett Syndrome Research Foundation. I gratefully acknowledge The Massachusetts Rett Syndrome Association for financial support.

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  1. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Woodruff Memorial Research Building–Room 7105B, 1639 Pierce Drive, Atlanta, 30322, GA, USA

    Paul A Wade

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Wade, P. Methyl CpG binding proteins: coupling chromatin architecture to gene regulation. Oncogene 20, 3166–3173 (2001). https://doi.org/10.1038/sj.onc.1204340

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