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首页> 外文期刊>Molecular and Cellular Biology >Variable Requirements for DNA-Binding Proteins at Polycomb-Dependent Repressive Regions in Human HOX Clusters
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Variable Requirements for DNA-Binding Proteins at Polycomb-Dependent Repressive Regions in Human HOX Clusters

机译：DNA结合蛋白在人类HOX簇中多梳依赖型抑制区的可变要求

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Polycomb group (PcG)-mediated repression is an evolutionarily conserved process critical for cell fate determination and maintenance of gene expression during embryonic development. However, the mechanisms underlying PcG recruitment in mammals remain unclear since few regulatory sites have been identified. We report two novel prospective PcG-dependent regulatory elements within the human HOXB and HOXC clusters and compare their repressive activities to a previously identified element in the HOXD cluster. These regions recruited the PcG proteins BMI1 and SUZ12 to a reporter construct in mesenchymal stem cells and conferred repression that was dependent upon PcG expression. Furthermore, we examined the potential of two DNA-binding proteins, JARID2 and YY1, to regulate PcG activity at these three elements. JARID2 has differential requirements, whereas YY1 appears to be required for repressive activity at all 3 sites. We conclude that distinct elements of the mammalian HOX clusters can recruit components of the PcG complexes and confer repression, similar to what has been seen in Drosophila. These elements, however, have diverse requirements for binding factors, which, combined with previous data on other loci, speaks to the complexity of PcG targeting in mammals.
机译：聚梳组（PcG）介导的抑制是一个进化保守的过程，对于胚胎发育过程中细胞命运的确定和基因表达的维持至关重要。然而，由于很少发现调控位点，因此在哺乳动物中募集PcG的基本机制仍不清楚。我们报告人类HOXB和HOXC群集中的两个新颖的预期的PcG依赖监管元素，并将其抑制活动与HOXD群集中以前确定的元素进行比较。这些区域将PcG蛋白BMI1和SUZ12募集到间充质干细胞中的报告基因构建体上，并赋予了依赖于PcG表达的抑制作用。此外，我们检查了两个DNA结合蛋白JARID2和YY1调节这三个元件上PcG活性的潜力。 JARID2具有不同的要求，而YY1似乎是所有3个位点的阻遏性活动所必需的。我们得出的结论是，哺乳动物HOX簇的不同元素可以募集PcG复合物的成分并赋予其抑制作用，类似于在果蝇中所见。然而，这些元件对结合因子有不同的要求，结合其他基因座的先前数据，这说明了在哺乳动物中靶向PcG的复杂性。

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