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nature----表观遗传学新思路


更新时间:2011-12-27



表观遗传学家们和生物信息学家们比较了干细胞的甲基化模式和神经元祖细胞(neuronal progenitor)的甲基化模式。搜寻关于大多数基因如何被调节的线索,他们发现DNA上含有特别少的甲基基团的区域。即低甲基化区域(low methylated regions, LMRs)在不同细胞类型之间存在差异,而且位于控制转录和细胞命运的基因区域中。进一步分析表明转录因子以一种定向的方式促成LMR模式出现。如果没有这些转录因子的作用,DNA依然保持甲基化和紧凑包装。并且,LMRs的动态是根据细胞的发育阶段发生变化。

“这些结果代表着思考模式的转移----转录因子控制细胞命运。”结合到DNA上的转录因子通过对DNA甲基化的影响留下特异性分子指纹。这些转录因子以一种定向的方式操纵DNA上表观遗传标记。这些表观遗传学“指纹”将有助于研究人员对细胞的历史及命运作出推论,从而能够简单地和可靠地鉴定出出错的细胞过程和蛋白。”有助于深入了解导致诸如癌症等疾病的分子机制及过程。

DNA-binding factors shape the mouse methylome at distal regulatory regions

Michael B. Stadler, Rabih Murr, Lukas Burger, et al.

Methylation of cytosines is an essential epigenetic modification in mammalian genomes, yet the rules that govern methylation patterns remain largely elusive. To gain insights into this process, we generated base-pair-resolution mouse methylomes in stem cells and neuronal progenitors. Advanced quantitative analysis identified low-methylated regions (LMRs) with an average methylation of 30%. These represent CpG-poor distal regulatory regions as evidenced by location, DNase I hypersensitivity, presence of enhancer chromatin marks and enhancer activity in reporter assays. LMRs are occupied by DNA-binding factors and their binding is necessary and sufficient to create LMRs. A comparison of neuronal and stem-cell methylomes confirms this dependency, as cell-type-specific LMRs are occupied by cell-type-specific transcription factors. This study provides methylome references for the mouse and shows that DNA-binding factors locally influence DNA methylation, enabling the identification of active regulatory regions.doi:10.1038/nature10716


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