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Methyl-CpG-binding domain proteins: readers of the epigenome

    Qian Du

    Epigenetics Research Laboratory, Genomics & Epigenetics Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia

    ,
    Phuc-Loi Luu

    Epigenetics Research Laboratory, Genomics & Epigenetics Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia

    ,
    Clare Stirzaker

    Epigenetics Research Laboratory, Genomics & Epigenetics Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia

    St Vincent's Clinical School, University of NSW, Darlinghurst, NSW 2010, Australia

    Authors contributed equally

    Search for more papers by this author

    &
    Susan J Clark,‡

    *Author for correspondence:

    E-mail Address: s.clark@garvan.org.au

    Epigenetics Research Laboratory, Genomics & Epigenetics Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia

    St Vincent's Clinical School, University of NSW, Darlinghurst, NSW 2010, Australia

    Authors contributed equally

    Search for more papers by this author

    Published Online:https://doi.org/10.2217/epi.15.39

    How DNA methylation is interpreted and influences genome regulation remains largely unknown. Proteins of the methyl-CpG-binding domain (MBD) family are primary candidates for the readout of DNA methylation as they recruit chromatin remodelers, histone deacetylases and methylases to methylated DNA associated with gene repression. MBD protein binding requires both functional MBD domains and methyl-CpGs; however, some MBD proteins also bind unmethylated DNA and active regulatory regions via alternative regulatory domains or interaction with the nucleosome remodeling deacetylase (NuRD/Mi-2) complex members. Mutations within MBD domains occur in many diseases, including neurological disorders and cancers, leading to loss of MBD binding specificity to methylated sites and gene deregulation. Here, we summarize the current state of knowledge about MBD proteins and their role as readers of the epigenome.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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