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G9a Histone Methyltransferase Contributes to Imprinting in the Mouse Placenta

机译:G9a组蛋白甲基转移酶有助于小鼠胎盘的印迹

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Whereas DNA methylation is essential for genomic imprinting, the importance of histone methylation in the allelic expression of imprinted genes is unclear. Imprinting control regions (ICRs), however, are marked by histone H3-K9 methylation on their DNA-methylated allele. In the placenta, the paternal silencing along the Kcnq1 domain on distal chromosome 7 also correlates with the presence of H3-K9 methylation, but imprinted repression at these genes is maintained independently of DNA methylation. To explore which histone methyltransferase (HMT) could mediate the allelic H3-K9 methylation on distal chromosome 7, and at ICRs, we generated mouse conceptuses deficient for the SET domain protein G9a. We found that in the embryo and placenta, the differential DNA methylation at ICRs and imprinted genes is maintained in the absence of G9a. Accordingly, in embryos, imprinted gene expression was unchanged at the domains analyzed, in spite of a global loss of H3-K9 dimethylation (H3K9me2). In contrast, the placenta-specific imprinting of genes on distal chromosome 7 is impaired in the absence of G9a, and this correlates with reduced levels of H3K9me2 and H3K9me3. These findings provide the first evidence for the involvement of an HMT and suggest that histone methylation contributes to imprinted gene repression in the trophoblast.
机译:尽管DNA甲基化对于基因组印迹是必不可少的,但不清楚组蛋白甲基化在印迹基因的等位基因表达中的重要性。但是,印迹控制区(ICR)的特征是其DNA甲基化的等位基因上的组蛋白H3-K9甲基化。在胎盘中,沿着远端染色体7上的 Kcnq1 结构域的父系沉默也与H3-K9甲基化的存在有关,但是这些基因上的印迹抑制与DNA甲基化无关。为了探索哪种组蛋白甲基转移酶(HMT)可以介导远端染色体7和ICR上的等位基因H3-K9甲基化,我们生成了SET结构域蛋白G9a缺失的小鼠conceptuses。我们发现在胚胎和胎盘中,在不存在G9a的情况下,ICR和印迹基因的DNA甲基化差异得以维持。因此,在胚胎中,尽管H3-K9甲基化(H3K9me2)的总体损失,但在所分析的域中,印迹基因表达没有变化。相反,在不存在G9a的情况下,远端7号染色体上基因的胎盘特异性印记受损,这与H3K9me2和H3K9me3的水平降低有关。这些发现为HMT的参与提供了第一个证据,并表明组蛋白甲基化有助于滋养细胞中印迹基因的抑制。

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