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首页> 外文期刊>Journal of cell biology >Large-Scale Chromatin Unfolding and Remodeling Induced by VP16 Acidic Activation Domain
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Large-Scale Chromatin Unfolding and Remodeling Induced by VP16 Acidic Activation Domain

机译：VP16酸性激活域诱导的大规模染色质展开和重塑

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Analysis of the relationship between transcriptional activators and chromatin organization has focused largely on lower levels of chromatin structure. Here we describe striking remodeling of large-scale chromatin structure induced by a strong transcriptional activator. A VP16-lac repressor fusion protein targeted the VP16 acidic activation domain to chromosome regions containing lac operator repeats. Targeting was accompanied by increased transcription, localized histone hyperacetylation, and recruitment of at least three different histone acetyltransferases. Observed effects on large-scale chromatin structure included unfolding of a 90-Mbp heterochromatic chromosome arm into an extended 25–40-μm chromonema fiber, remodeling of this fiber into a novel subnuclear domain, and propagation of large-scale chromatin unfolding over hundreds of kilobase pairs. These changes in large-scale chromatin structure occurred even with inhibition of ongoing transcription by α-amanitin. Our results suggest a functional link between recruitment of the transcriptional machinery and changes in large-scale chromatin structure. Based on the observed long-range propagation of changes in large-scale chromatin structure, we suggest a possible rationale for the observed clustering of housekeeping genes within Mbp-sized chromosome bands.
机译：转录激活因子与染色质组织之间的关系分析主要集中在较低水平的染色质结构上。在这里，我们描述了由强转录激活剂诱导的大规模染色质结构的惊人重塑。 VP16-lac阻遏物融合蛋白将VP16酸性激活结构域靶向含有lac操纵子重复序列的染色体区域。靶向伴随着增加的转录，局部的组蛋白超乙酰化和募集至少三种不同的组蛋白乙酰转移酶。观察到的对大规模染色质结构的影响包括：将一个90 Mbp的异色染色体臂展开为一个扩展的25–40μm染色体细胞，将该纤维重塑为一个新的亚核结构域，以及大规模染色质的传播超过数百个千碱基对。即使抑制了α-amanitin正在进行的转录，大规模染色质结构的这些变化也会发生。我们的结果表明转录机制的募集与大规模染色质结构变化之间的功能联系。基于观察到的大规模染色质结构变化的远距离传播，我们为观察到的Mbp大小的染色体带内看家基因的聚类提出了可能的理论依据。

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