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Maintenance of DNA methylation: Dnmt3b joins the dance

机译:维持DNA甲基化:Dnmt3b参与其中

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DNA methylation mainly occurs within the context of CpG dinucleotides and is essential for embryonic development and gene repression. It is generally accepted that DNA methyltransferases (Dnmt) carry out specific and non-overlapping functions: Dnmt3a and Dnmt3b being responsible for the establishment of methylation around the time of implantation and Dnmtl ensuring that methylation is faithfully copied to daughter cells (maintenance methylation). However, this model may be too simple. There is evidence to suggest that Dnmtl alone is incapable of a perfect maintenance of methylation, and that the de novo enzymes Dnmt3a and Dnmt3b contribute to the maintenance of DNA methylation as well. Dr. Claire Francastel and colleagues previously reported that certain germ line genes are specific targets of Dnmt3b, and that Dnmt3b remains bound to their promoter regions in somatic cells via interaction with the transcriptional repressor E2F6. In their new paper, the authors present additional data suggesting a continuing role for Dnmt3b in the methylation of germ line genes also in somatic cells. They found that maintenance of methylation and subsequent silencing of a handful of germ line genes require Dnmt3b but not Dnmtl, suggesting a new role for Dnmt3b in the protection of somatic cells against the promiscuous expression of the germ line program. Given the increasing number of tumour cells exhibiting catalytically inactive Dnmt3b enzyme, the observation that this enzyme might be required to maintain a number of germ line specific genes in a silent state is of particular interest in the field of carcinogenesis.
机译:DNA甲基化主要发生在CpG二核苷酸的背景下,对于胚胎发育和基因阻抑至关重要。通常公认的是DNA甲基转移酶(Dnmt)具有特定且不重叠的功能:Dnmt3a和Dnmt3b负责在植入时建立甲基化,而Dnmt1确保将甲基化忠实复制到子细胞中(维持甲基化)。但是,此模型可能太简单了。有证据表明,单独的Dnmtl不能完全维持甲基化,并且从头酶Dnmt3a和Dnmt3b也有助于维持DNA甲基化。 Claire Francastel博士及其同事先前报道,某些种系基因是Dnmt3b的特异性靶标,并且Dnmt3b通过与转录阻遏物E2F6的相互作用,仍与体细胞中的启动子区域结合。在他们的新论文中,作者们提供了其他数据,表明Dnmt3b在体细胞中的种系基因甲基化中也继续发挥作用。他们发现维持甲基化和随后沉默少数种系基因需要Dnmt3b,但不需要Dnmtl,这表明Dnmt3b在保护体细胞免受种系程序的混杂表达方面具有新的作用。鉴于越来越多的肿瘤细胞表现出催化失活的Dnmt3b酶,这种观察可能需要将这种酶维持许多种系特异性基因处于沉默状态,这一发现在致癌领域特别受关注。

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