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首页> 外文期刊>Genome Research >Elucidation of the ELK1 target gene network reveals a role in the coordinate regulation of core components of the gene regulation machinery
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Elucidation of the ELK1 target gene network reveals a role in the coordinate regulation of core components of the gene regulation machinery

机译:ELK1目标基因网络的阐明揭示了在基因调控机制核心组件的协调调控中的作用

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摘要

Transcription factors play an important role in orchestrating the activation of specific networks of genes through targeting their proximal promoter and distal enhancer regions. However, it is unclear how the specificity of downstream responses is maintained by individual members of transcription-factor families and, in most cases, what their target repertoire is. We have used ChIP-chip analysis to identify the target genes of the ETS-domain transcription factor ELK1. Two distinct modes of ELK1 target gene selection are identified; the first involves redundant promoter binding with other ETS-domain family members; the second occurs through combinatorial binding with a second transcription factor SRF, which specifies a unique group of target genes. One of the most prominent groups of genes forming the ELK1 target network includes classes involved in core gene expression control, namely, components of the basal transcriptional machinery, the spliceosome and the ribosome. Amongst the set of genes encoding the basal transcription machinery components, are a functionally linked subset of GTFs and TAFs. Our study, therefore, reveals an unsuspected level of coordinate regulation of components of the core gene expression control machinery and also identifies two different modes of promoter targeting through binding with a second transcription factor or redundant binding with other ETS-domain family members.
机译:转录因子在靶向特定基因网络的近端启动子和远端增强子区域的激活中起着重要作用。但是,尚不清楚转录因子家族的各个成员如何维持下游反应的特异性,并且在大多数情况下,它们的目标库是什么。我们已经使用ChIP芯片分析来确定ETS域转录因子ELK1的目标基因。确定了ELK1靶基因选择的两种不同模式:首先涉及与其他ETS结构域家族成员的冗余启动子结合;第二种是通过与第二种转录因子SRF的组合结合而发生的,后者指定了一组独特的靶基因。形成ELK1靶标网络的最突出的基因组之一包括与核心基因表达控制有关的类,即基础转录机制,剪接体和核糖体的组成部分。在编码基础转录机制组成部分的一组基因中,有一个功能连接的GTF和TAF。因此,我们的研究揭示了核心基因表达控制机制各组成部分的协调调控水平达到意想不到的水平,并且通过与第二个转录因子结合或与其他ETS结构域家族成员的冗余结合,鉴定了两种不同的启动子靶向模式。

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  • 来源
    《Genome Research》 |2009年第11期|1963-1973|共11页
  • 作者单位

    Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom;

    Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom;

    Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom;

    Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom;

    Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom;

    Division of Molecular and Cellular Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA;

    Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard School of Public Health, Boston, Massachusetts 02115, USA;

    Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard School of Public Health, Boston, Massachusetts 02115, USA;

    Division of Molecular and Cellular Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA;

    Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom;

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