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Genetic alterations of DNA methylation machinery in human diseases

    Tewfik Hamidi

    Department of Epigenetics & Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park – Research Division, 1808 Park Road 1C, P. O. Box 389, Smithville, TX 78957, USA

    Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Science Park, 1808 Park Road 1C, Smithville, TX 78957, USA

    Authors contributed equally

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    ,
    Anup Kumar Singh

    Department of Epigenetics & Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park – Research Division, 1808 Park Road 1C, P. O. Box 389, Smithville, TX 78957, USA

    Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Science Park, 1808 Park Road 1C, Smithville, TX 78957, USA

    Authors contributed equally

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    &
    Taiping Chen

    *Author for correspondence:

    E-mail Address: tchen2@mdanderson.org

    Department of Epigenetics & Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park – Research Division, 1808 Park Road 1C, P. O. Box 389, Smithville, TX 78957, USA

    Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Science Park, 1808 Park Road 1C, Smithville, TX 78957, USA

    The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, USA

    Published Online:https://doi.org/10.2217/epi.14.80

    DNA methylation plays a critical role in the regulation of chromatin structure and gene expression and is involved in a variety of biological processes. The levels and patterns of DNA methylation are regulated by both DNA methyltransferases (DNMT1, DNMT3A and DNMT3B) and ‘demethylating’ proteins, including the ten-eleven translocation (TET) family of dioxygenases (TET1, TET2 and TET3). The effects of DNA methylation on chromatin and gene expression are largely mediated by methylated DNA ‘reader’ proteins, including MeCP2. Numerous mutations in DNMTs, TETs and MeCP2 have been identified in cancer and developmental disorders, highlighting the importance of the DNA methylation machinery in human development and physiology. In this review, we describe these mutations and discuss how they may lead to disease phenotypes.

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

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