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首页> 外文期刊>The FEBS journal >Recruitment of transcription complexes to the beta-globin locus control region and transcription of hypersensitive site 3 prior to erythroid differentiation of murine embryonic stem cells
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Recruitment of transcription complexes to the beta-globin locus control region and transcription of hypersensitive site 3 prior to erythroid differentiation of murine embryonic stem cells

机译:招募转录复合物到β-球蛋白基因座控制区和超敏位点3的转录,然后进行鼠胚胎干细胞的红系分化

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摘要

Eukaryotic chromosomal DNA is densely packaged in the nucleus and organized into discrete domains of active and inactive chromatin. Gene loci that are activated during the process of cell differentiation undergo changes that result in modifications of specific histone tail residues and in loosening of chromatin structure. The beta-globin genes are expressed exclusively in erythroid cells. High-level expression of these genes is mediated by a locus control region (LCR), a powerful DNA regulatory element composed of several DNase I hypersensitive (HS) sites and located far upstream of the beta-globin genes. Here we show that RNA polymerase II and specific histone modifications that mark transcriptionally active chromatin domains are associated with the LCR core elements HS2 and HS3 in murine embryonic stem cells prior to differentiation along the erythroid lineage. At this stage HS3 is abundantly transcribed. After in vitro differentiation, RNA Polymerase II can also be detected at the embryonic epsilon- and adult beta-globin genes. These results are consistent with the hypothesis that activation of the beta-globin gene locus is initiated by protein complexes recruited to the LCR.
机译:真核染色体DNA紧密地包装在细胞核中,并组织成有活性和无活性染色质的离散域。在细胞分化过程中被激活的基因座经历了变化,这些变化导致特定组蛋白尾部残基的修饰和染色质结构的松弛。 β-珠蛋白基因仅在类红细胞中表达。这些基因的高水平表达是由基因座控制区(LCR)介导的,该区域是一个强大的DNA调控元件,由多个DNase I超敏(HS)位点组成,并且位于β-珠蛋白基因的上游。在这里,我们显示RNA聚合酶II和标记转录活性染色质域的特定组蛋白修饰与鼠胚胎干细胞中的LCR核心元件HS2和HS3相关联,然后沿红系谱系分化。在此阶段,HS3被大量转录。在体外分化后,还可以在胚胎的ε-和成人β-珠蛋白基因处检测到RNA聚合酶II。这些结果与以下假设一致:β-珠蛋白基因基因座的激活是由募集到LCR的蛋白质复合物引发的。

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