The euchromatic and heterochromatic landscapes are shaped by antagonizing effects of transcription on H2A.Z deposition.

The euchromatic and heterochromatic landscapes are shaped by antagonizing effects of transcription on H2A.Z deposition.
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DOI:
10.1371/journal.pgen.1000687
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发表时间:
2009-10
期刊:
影响因子:
4.5
通讯作者:
Robert F
Robert F
中科院分区:
生物学2区
文献类型:
--
作者:
Hardy S;Jacques PE;Gévry N;Forest A;Fortin ME;Laflamme L;Gaudreau L;Robert F

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变异组蛋白H2A的作用。Z在基因表达中的作用现在已经得到了很好的证实,但人们对它的作用机制知之甚少。结合ChIP-chip、敲低和表达谱实验,我们发现在基因诱导下,人类H2A。Z与基因启动子结合,帮助募集转录机制。令人惊讶的是,我们还发现了H2A。Z在基因组中以低水平随机结合,活性转录在转录区拮抗这种结合。停止转录后,随机H2A。Z很快重新出现在基因上,表明这种结合利用了一种活跃的机制。在兼性异染色质中,我们观察到变异组蛋白的高度积累,这可能是由于这些区域缺乏转录。这些结果显示了染色质结构和转录如何相互拮抗,从而形成染色质并控制基因表达。活细胞中的DNA被组蛋白和非组蛋白包装成染色质。这种包装是非常动态的,允许调控蛋白(如转录因子)进入DNA。大多数染色质都包裹着所谓的规范组蛋白;即H2A, H2B, H3, H4。然而,在某些区域,变异组蛋白取代标准组蛋白,形成特殊的染色质区域。这里我们展示了变异组蛋白H2A。Z被动态募集到启动子区域,在那里它帮助募集RNA聚合酶II,这种酶负责基因表达的第一步。此外,我们表明H2A。Z也在基因组中随机结合,但这些分子在RNA聚合酶II的传递过程中被移除。在非转录区,H2A。Z聚集在称为异染色质的大区域中。我们建议在随机H2A之间进行一场战斗。Z沉积和rnapii依赖性H2A。Z型驱逐形成了染色质景观。
A role for variant histone H2A.Z in gene expression is now well established but little is known about the mechanisms by which it operates. Using a combination of ChIP–chip, knockdown and expression profiling experiments, we show that upon gene induction, human H2A.Z associates with gene promoters and helps in recruiting the transcriptional machinery. Surprisingly, we also found that H2A.Z is randomly incorporated in the genome at low levels and that active transcription antagonizes this incorporation in transcribed regions. After cessation of transcription, random H2A.Z quickly reappears on genes, demonstrating that this incorporation utilizes an active mechanism. Within facultative heterochromatin, we observe a hyper accumulation of the variant histone, which might be due to the lack of transcription in these regions. These results show how chromatin structure and transcription can antagonize each other, therefore shaping chromatin and controlling gene expression. DNA in living cells is packaged into chromatin by histones and non-histone proteins. This packaging is very dynamic, allowing the controlled access of regulatory proteins such as transcription factors to DNA. Most chromatin is packaged with so-called canonical histones; namely H2A, H2B, H3, and H4. In some regions, however, variant histones replace canonical histones, creating special chromatin regions. Here we show that the variant histone H2A.Z is dynamically recruited to promoter regions where it helps in the recruitment of RNA polymerase II, the enzyme responsible for the first step of gene expression. In addition, we show that H2A.Z also associates randomly in the genome, but these molecules are removed during the passage of RNA polymerase II. In non-transcribed regions, H2A.Z accumulates in large domains called heterochromatin. We propose that a battle between random H2A.Z deposition and RNAPII-dependent H2A.Z eviction shapes the chromatin landscape.
过乙酰化形式的替换组蛋白H2A.Z是鸡肉中活性基因的特征。
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