Targeting epigenetic regulations in cancer.
Epigenetic regulation of gene expression is a dynamic and reversible process with DNA methylation, histone modifications, and chromatin remodeling. Recently, groundbreaking studies have demonstrated the importance of DNA and chromatin regulatory proteins from different aspects, including stem cell, development, and tumor genesis. Abnormal epigenetic regulation is frequently associated with diseases and drugs targeting DNA methylation and histone acetylation have been approved for cancer therapy. Although the network of epigenetic regulation is more complex than people expect, new potential druggable chromatin-associated proteins are being discovered and tested for clinical application. Here we review the key proteins that mediate epigenetic regulations through DNA methylation, the acetylation and methylation of histones, and the reader proteins that bind to modified histones. We also discuss cancer associations and recent progress of pharmacological development of these proteins.
Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA.
Bo
B
Ning
Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA Xiangya Hospital, Xiangya School of Medicine, Central South University, Changsha 410008, China.
Wenyuan
W
Li
Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA.
Wei
W
Zhao
Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA Department of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, NY 10065, USA rwang3@houstonmethodist.org.
Rongfu
R
Wang
D000107:Acetylation; D000818:Animals; D002843:Chromatin / Q000378:metabolism; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D042421:Histone Code; D006657:Histones / Q000378:metabolism; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D014158:Transcription, Genetic
D002843:Chromatin; D006657:Histones; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases
DNA methylation; anti-cancer drugs; epigenetic regulation; histone modification; inhibitors