Estrogen receptor-α directs ordered, cyclical, and combinatorial recruitment of cofactors on a natural target promoter
Estrogen receptor-α directs ordered, cyclical, and combinatorial recruitment of cofactors on a natural target promoter
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DOI：
10.1016/s0092-8674(03)00934-6
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发表时间：
2003-12-12
期刊：
影响因子：
64.5
通讯作者：
Gannon, F
中科院分区：
文献类型：
--
作者：
Métivier, R;Penot, G;Gannon, F
基因的转录激活涉及基础转录机制和中间因子的组分的精心策划的募集，伴随着由组蛋白尾部的翻译后修饰和核小体重塑产生的局部染色质结构的改变。我们在这里提供了一个全面的图片事件导致转录激活的基因，通过评估雌激素受体α（NR 3A 1）靶pS2基因启动子在MCF-7细胞。这种描述集成了染色质重塑与动力学评价的46个转录因子与启动子的关联的循环网络，如染色质免疫沉淀测定。我们定义了一个“转录时钟”的概念，指导和实现的顺序和组合组装的转录生产复合物的启动子。此外，组蛋白去乙酰化酶和核小体重塑复合物在限制转录中的关键作用的意外发现意味着转录激活是一个循环过程，需要激活和抑制表观遗传过程。
Transcriptional activation of a gene involves an orchestrated recruitment of components of the basal transcription machinery and intermediate factors, concomitant with an alteration in local chromatin structure generated by posttranslational modifications of histone tails and nucleosome remodeling. We provide here a comprehensive picture of events resulting in transcriptional activation of a gene, through evaluating the estrogen receptor-alpha (NR3A1) target pS2 gene promoter in MCF-7 cells. This description integrates chromatin remodeling with a kinetic evaluation of cyclical networks of association of 46 transcription factors with the promoter, as determined by chromatin immunoprecipitation assays. We define the concept of a "transcriptional clock" that directs and achieves the sequential and combinatorial assembly of a transcriptionally productive complex on a promoter. Furthermore, the unanticipated findings of key roles for histone deacetylases and nucleosome-remodeling complexes in limiting transcription implies that transcriptional activation is a cyclical process that requires both activating and repressive epigenetic processes.