Large, male germ cell-specific hypomethylated DNA domains with unique genomic and epigenomic features on the mouse X chromosome.

Large, male germ cell-specific hypomethylated DNA domains with unique genomic and epigenomic features on the mouse X chromosome.
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在小鼠X染色体上具有独特的基因组和表观基因组特征的大型男性生殖细胞特异性DNA结构域。

DOI:
10.1093/dnares/dst030
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发表时间:
2013-12
期刊:
DNA research : an international journal for rapid publication of reports on genes and genomes
影响因子:
--
通讯作者:
Abe K
Abe K
中科院分区:
其他
文献类型:
--
作者:
Ikeda R;Shiura H;Numata K;Sugimoto M;Kondo M;Mise N;Suzuki M;Greally JM;Abe K

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为了了解小鼠生殖细胞特异性基因表达所需的表观遗传调控,我们使用适用于少量细胞的基于微阵列的测定分析了发育中生殖细胞的DNA甲基化谱。分析揭示了测试的细胞类型之间的差异甲基化位点。在这里,我们重点关注了一组专门在种系细胞中低甲基化的基因组序列,作为参与种系基因表达表观遗传调节的候选区域。这些低甲基化的序列倾向于成簇,形成大的(10 kb至109 Mb)基因组结构域,特别是在雄性生殖细胞的X染色体上。这些区域中的大多数,在此称为大的低甲基化结构域(LoD),对应于含有显示生殖细胞或睾丸特异性表达的基因家族的片段重复区域,包括癌症睾丸抗原基因。我们发现DNA甲基化水平与这些结构域中基因的表达呈负相关。大多数LoD似乎富含H3赖氨酸9二甲基化,通常被认为是一种抑制性组蛋白修饰,尽管一些LoD基因可以在雄性生殖细胞中表达。因此,似乎与LoD相关的这种独特的表观基因组状态可能构成这些基因组结构域中所含基因的特异性表达的基础。
To understand the epigenetic regulation required for germ cell-specific gene expression in the mouse, we analysed DNA methylation profiles of developing germ cells using a microarray-based assay adapted for a small number of cells. The analysis revealed differentially methylated sites between cell types tested. Here, we focused on a group of genomic sequences hypomethylated specifically in germline cells as candidate regions involved in the epigenetic regulation of germline gene expression. These hypomethylated sequences tend to be clustered, forming large (10 kb to ∼9 Mb) genomic domains, particularly on the X chromosome of male germ cells. Most of these regions, designated here as large hypomethylated domains (LoDs), correspond to segmentally duplicated regions that contain gene families showing germ cell- or testis-specific expression, including cancer testis antigen genes. We found an inverse correlation between DNA methylation level and expression of genes in these domains. Most LoDs appear to be enriched with H3 lysine 9 dimethylation, usually regarded as a repressive histone modification, although some LoD genes can be expressed in male germ cells. It thus appears that such a unique epigenomic state associated with the LoDs may constitute a basis for the specific expression of genes contained in these genomic domains.
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