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Readers of DNA methylation, the MBD family as potential therapeutic targets
Pharmacology & Therapeutics ( IF 13.5 ) Pub Date : 2017-11-08 , DOI: 10.1016/j.pharmthera.2017.11.002
Gordon D. Ginder , David C. Williams

DNA methylation represents a fundamental epigenetic modification that regulates chromatin architecture and gene transcription. Many diseases, including cancer, show aberrant methylation patterns that contribute to the disease phenotype. DNA methylation inhibitors have been used to block methylation dependent gene silencing to treat hematopoietic neoplasms and to restore expression of developmentally silenced genes. However, these inhibitors disrupt methylation globally and show significant off-target toxicities. As an alternative approach, we have been studying readers of DNA methylation, the 5-methylcytosine binding domain family of proteins, as potential therapeutic targets to restore expression of aberrantly and developmentally methylated and silenced genes. In this review, we discuss the role of DNA methylation in gene regulation and cancer development, the structure and function of the 5-methylcytosine binding domain family of proteins, and the possibility of targeting the complexes these proteins form to treat human disease.



中文翻译:

DNA甲基化的读者,MBD家族可作为潜在的治疗靶标

DNA甲基化代表基本的表观遗传修饰,可调节染色质结构和基因转录。许多疾病,包括癌症,都表现出异常的甲基化模式,从而导致了疾病的表型。DNA甲基化抑制剂已用于阻断甲基化依赖性基因沉默,以治疗造血肿瘤并恢复发育沉默基因的表达。然而,这些抑制剂在全球范围内破坏了甲基化并显示出明显的脱靶毒性。作为一种替代方法,我们一直在研究DNA甲基化(蛋白质的5甲基胞嘧啶结合域家族)的读者,作为恢复异常和发育中的甲基化和沉默基因表达的潜在治疗靶标。在这篇评论中,

更新日期:2017-11-08
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