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首页> 外文期刊>Molecular and Cellular Biology >The Thymine DNA Glycosylase MBD4 Represses Transcription and Is Associated with Methylated p16INK4a and hMLH1 Genes
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The Thymine DNA Glycosylase MBD4 Represses Transcription and Is Associated with Methylated p16INK4a and hMLH1 Genes

机译：胸腺嘧啶脱氧核糖核酸糖基化酶MBD4抑制转录并与甲基化的p16INK4a和hMLH1基因相关

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摘要

Epigenetic silencing through methyl-CpG (mCpG) is implicated in many biological patterns such as genome imprinting, X chromosome inactivation, and cancer development. In this process, the mCpG binding domain (MBD) proteins play an essential role in transmitting epigenetic information to downstream regulatory proteins. Among the five MBD proteins identified so far, MBD4 has been the only exception; it has long been thought to be a DNA repair protein. Herein we demonstrate that MBD4 has the ability to repress transcription through mCpG. Transcriptional repression by the MBD4 is histone deacetylase (HDAC) dependent, and MBD4 directly binds to Sin3A and HDAC1 at three central regions that overlap transcriptional repression domains. Furthermore, a chromatin immunoprecipitation assay clearly shows that MBD4 binds to hypermethylated promoters of the p16INK4a and hMLH1 genes. These results suggest that MBD4 is one of the essential components involved in epigenetic silencing in cancer and its repair activity is necessary for the maintenance of hypermethylated promoters.
机译：通过甲基CpG（mCpG）进行的表观遗传沉默与许多生物学模式有关，例如基因组印迹，X染色体失活和癌症发展。在此过程中，mCpG结合域（MBD）蛋白在将表观遗传信息传递至下游调节蛋白中起着至关重要的作用。在目前鉴定的五种MBD蛋白中，MBD4是唯一的例外。长期以来，人们一直认为它是一种DNA修复蛋白。在本文中，我们证明了MBD4具有通过mCpG抑制转录的能力。 MBD4的转录抑制是组蛋白脱乙酰基酶（HDAC）依赖性的，MBD4在与转录抑制域重叠的三个中心区域直接结合Sin3A和HDAC1。此外，染色质免疫沉淀实验清楚地表明MBD4与 p16 INK4a 和 hMLH1 基因的超甲基化启动子结合。这些结果表明，MBD4是参与癌症表观遗传沉默的必需成分之一，其修复活性对于维持高甲基化启动子是必需的。

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