Large-scale chromatin unfolding and remodeling induced by VP16 acidic activation domain.
Large-scale chromatin unfolding and remodeling induced by VP16 acidic activation domain.
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VP16酸性活化域诱导的大规模染色质展开和重塑。
DOI：
10.1083/jcb.145.7.1341
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发表时间：
1999-06-28
影响因子：
7.8
通讯作者：
Belmont, A S
中科院分区：
文献类型：
--
作者：
Tumbar, T;Sudlow, G;Belmont, A S
转录激活因子和染色质组织之间的关系的分析主要集中在较低水平的染色质结构。在这里，我们描述了一个强大的转录激活剂诱导的大规模染色质结构的显着重塑。VP 16-lac阻遏物融合蛋白将VP 16酸性激活结构域靶向至含有lac操纵子重复的染色体区域。靶向伴随着转录增加，局部组蛋白乙酰化，和招募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90-Mbp异染色质染色体臂展开为延伸的25-40-μm染色丝纤维，该纤维重塑为新的亚核结构域，以及大规模染色质展开在数百个酶对上的传播。即使α-鹅膏毒肽抑制了正在进行的转录，也会发生大规模染色质结构的这些变化。我们的研究结果表明，招聘的转录机制和大规模的染色质结构的变化之间的功能联系。基于所观察到的大规模染色质结构的变化的长距离传播，我们提出了一个可能的理由观察到的Mbp大小的染色体带内的管家基因的聚类。
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.