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首页> 外文期刊>Molecular and Cellular Biology >A Human Globin Enhancer Causes both Discrete and Widespread Alterations in Chromatin Structure
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A Human Globin Enhancer Causes both Discrete and Widespread Alterations in Chromatin Structure

机译：人类球蛋白增强剂会导致染色质结构的离散和广泛变化

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Gene activation requires alteration of chromatin structure to facilitate active transcription complex formation at a gene promoter. Nucleosome remodeling complexes and histone modifying complexes each play unique and interdependent roles in bringing about these changes. The role of distant enhancers in these structural alterations is not well understood. We studied nucleosome remodeling and covalent histone modification mediated by the β-globin locus control region HS2 enhancer at nucleosome-level resolution throughout a 5.5-kb globin gene model locus in vivo in K562 cells. We compared the transcriptionally active locus to one in which HS2 was inactivated by mutations in the core NF-E2 sites. In contrast to inactive templates, nucleosomes were mobilized in discrete areas of the active locus, including the HS2 core and the proximal promoter. Large differences in restriction enzyme accessibility between the active and inactive templates were limited to the regions of nucleosome mobilization, which subsumed the DNase I hypersensitive sites. In contrast to this discrete pattern, histone H3 and H4 acetylation and H3 K4 methylation were elevated across the entire active locus, accompanied by depletion of linker histone H1. The coding region of the gene differed from the regulatory regions, demonstrating both nucleosome mobilization and histone hyperacetylation, but lacked differences in restriction enzyme accessibility between transcriptionally active and inactive genes. Thus, although the histone modification pattern we observe is consistent with the spreading of histone modifying activity from the distant enhancer, the pattern of nucleosome mobilization is more compatible with direct contact between an enhancer and promoter.
机译：基因激活需要改变染色质结构，以促进基因启动子上活性转录复合物的形成。核小体重塑复合物和组蛋白修饰复合物在实现这些变化中各自发挥独特且相互依存的作用。远距离增强子在这些结构改变中的作用尚不清楚。我们研究了在K562细胞中体内5.5-kb球蛋白基因模型基因座中，由β-球蛋白基因座控制区HS2增强子介导的核小体重塑和共价组蛋白修饰，其核小体水平的分辨率。我们将转录活性基因座与HS2被核心NF-E2位点突变灭活的基因座进行了比较。与非活性模板相反，核小体被动员在活性基因座的离散区域，包括HS2核心和近端启动子。活性和非活性模板之间限制酶可及性的巨大差异仅限于核小体动员区域，该区域包括DNase I超敏位点。与这种离散模式相反，在整个活性基因座中，组蛋白H3和H4乙酰化以及H3 K4甲基化升高，同时连接子组蛋白H1耗尽。该基因的编码区不同于调节区，表明核小体动员和组蛋白超乙酰化，但在转录活性和非活性基因之间限制酶可及性方面缺乏差异。因此，尽管我们观察到的组蛋白修饰模式与来自远距离增强子的组蛋白修饰活性的分布是一致的，但核小体动员的模式与增强子和启动子之间的直接接触更相容。

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