Nonallelic Transcriptional Roles of CTCF and Cohesins at Imprinted Loci
Nonallelic Transcriptional Roles of CTCF and Cohesins at Imprinted Loci
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DOI：
10.1128/mcb.01449-10
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发表时间：
2011-08-01
影响因子：
5.3
通讯作者：
Bartolomei, Marisa S.
中科院分区：
文献类型：
--
作者：
Lin, Shu;Ferguson-Smith, Anne C.;Bartolomei, Marisa S.
粘着蛋白复合体将姐妹染色单体连接在一起，并且对于染色体分离是必需的。最近，cohesins已被牵连在转录调控和绝缘通过全基因组共定位与绝缘子蛋白CTCF，包括参与印记H19/Igf 2基因座。CTCF结合到多个印迹基因座，并且是在H19/Igf 2基因座处正确印迹表达所需的。在这里，我们报告说，cohesins共定位与CTCF在两个额外的印迹位点，Dlk 1-Dio 3和Kcnq 1/Kcnq 1 ot 1位点。类似于H19/Igf 2基因座，CTCF和粘着蛋白优先结合未甲基化的母体等位基因上的Gt 12差异甲基化区域（DMR）。为了确定CTCF和粘附素在三个印迹位点处的结合的功能重要性，在小鼠胚胎成纤维细胞中耗尽CTCF和粘附素。在这三个位点的印记基因的单等位基因表达保持。然而，这些基因的mRNA水平通常增加;对于H19和Igf 2，表达水平的增加与印迹控制区中的CTCF结合位点无关。这些实验的结果表明CTCF和cohesins在体细胞中抑制印迹基因中的未被重视的作用。
The cohesin complex holds sister chromatids together and is essential for chromosome segregation. Recently, cohesins have been implicated in transcriptional regulation and insulation through genome-wide colocalization with the insulator protein CTCF, including involvement at the imprinted H19/Igf2 locus. CTCF binds to multiple imprinted loci and is required for proper imprinted expression at the H19/Igf2 locus. Here we report that cohesins colocalize with CTCF at two additional imprinted loci, the Dlk1-Dio3 and the Kcnq1/Kcnq1ot1 loci. Similar to the H19/Igf2 locus, CTCF and cohesins preferentially bind to the Gtl2 differentially methylated region (DMR) on the unmethylated maternal allele. To determine the functional importance of the binding of CTCF and cohesins at the three imprinted loci, CTCF and cohesins were depleted in mouse embryonic fibroblast cells. The monoallelic expression of imprinted genes at these three loci was maintained. However, mRNA levels for these genes were typically increased; for H19 and Igf2 the increased level of expression was independent of the CTCF-binding sites in the imprinting control region. Results of these experiments demonstrate an unappreciated role for CTCF and cohesins in the repression of imprinted genes in somatic cells.