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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >The ISWI ATPase Snf2h is required for early mouse development
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The ISWI ATPase Snf2h is required for early mouse development

机译：ISWI ATPase Snf2h是早期小鼠发育所必需的

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摘要

Chromatin assembly and remodeling complexes alter histone-DNA interactions by using the energy of ATP hydrolysis catalyzed by nucleosome-dependent ATPase subunits. Several classes of ATP-dependent chromatin remodeling complexes exist, including the ISWI family. ISWI complexes disrupt histone-DNA interactions in vitro by facilitating nucleosome sliding. Snf2h is a widely expressed ISWI ATPase. We investigated the role of the Snf2h gene in mammalian development by generating a null mutation in mice. Snf2h heterozygous mutant mice are born at the expected frequency and appear normal. Snf2h~(-/-) embryos die during the periimplantation stage. Blastocyst outgrowth experiments indicate that loss of Snf2h results in growth arrest and cell death of both the trophectoderm and inner cell mass. To investigate the effect of decreased Snf2h levels in adult cells, we performed antisense inhibition of Snf2h in human hematopoietic progenitors. Reducing Snf2h levels inhibited CD34~+ progenitors from undergoing cytokine-induced erythropoiesis in vitro. Our results indicate that Snf2h is required for proliferation of early blastocyst-derived stem cells and adult human hematopoietic progenitors. Cells lacking Snf2h are thus prevented from further embryonic development and differentiation.
机译：染色质组装和重塑复合物通过利用核小体依赖性ATPase亚基催化的ATP水解能量来改变组蛋白与DNA的相互作用。存在几类ATP依赖的染色质重塑复合物，包括ISWI家族。 ISWI复合物通过促进核小体滑动而在体外破坏组蛋白与DNA的相互作用。 Snf2h是一种广泛表达的ISWI ATPase。我们通过在小鼠中产生空突变来研究Snf2h基因在哺乳动物发育中的作用。 Snf2h杂合突变小鼠以预期的频率出生并且看起来正常。 Snf2h〜（-/-）胚胎在植入期周围死亡。胚泡增生实验表明，Snf2h的丧失导致滋养外胚层和内部细胞团的生长停滞和细胞死亡。为了研究成年细胞中Snf2h水平降低的影响，我们对人类造血祖细胞中Snf2h进行了反义抑制。降低Snf2h水平可抑制CD34〜+祖细胞在体外受到细胞因子诱导的红细胞生成。我们的结果表明，Snf2h是早期胚泡衍生干细胞和成年人类造血祖细胞增殖所必需的。因此可以防止缺少Snf2h的细胞进一步胚胎发育和分化。

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