Intergenic Transcription, Cell-Cycle and the Developmentally Regulated Epigenetic Profile of the Human Beta-Globin Locus

Intergenic Transcription, Cell-Cycle and the Developmentally Regulated Epigenetic Profile of the Human Beta-Globin Locus
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DOI:
10.1371/journal.pone.0000630
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发表时间:
2007-07-18
期刊:
影响因子:
3.7
通讯作者:
Fraser, Peter
Fraser, Peter
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Miles, Joanne;Mitchell, Jennifer A.;Fraser, Peter

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一些证据已经建立了转录活性和组蛋白的特异性翻译后修饰之间的紧密联系。在这里,我们使用RNA FISH,在红系细胞中,在人类β-珠蛋白基因座的基因间转录发生在一个区域大于250 kb,包括附近的嗅觉受体基因簇中的几个基因。整个区域在细胞周期的S期转录。然而,在该区域内,存在类似于20 kb的高基因间转录的亚结构域,其发生在S期之外。这些亚结构域在发育上受到调节,并富含主要对组蛋白H3的高水平活性修饰。亚结构域对应于β-珠蛋白基因座控制区,其在红系细胞中的所有发育阶段都是活性的,以及发育调节的活性珠蛋白基因侧翼的区域。这些结果将高水平的非S期基因间转录与组蛋白H3的全域活性组蛋白修饰相关联。
Several lines of evidence have established strong links between transcriptional activity and specific post-translation modifications of histones. Here we show using RNA FISH that in erythroid cells, intergenic transcription in the human beta-globin locus occurs over a region of greater than 250 kb including several genes in the nearby olfactory receptor gene cluster. This entire region is transcribed during S phase of the cell cycle. However, within this region there are similar to 20 kb sub-domains of high intergenic transcription that occurs outside of S phase. These sub-domains are developmentally regulated and enriched with high levels of active modifications primarily to histone H3. The sub-domains correspond to the beta-globin locus control region, which is active at all developmental stages in erythroid cells, and the region flanking the developmentally regulated, active globin genes. These results correlate high levels of non-S phase intergenic transcription with domain-wide active histone modifications to histone H3.