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Enhancer-core-promoter specificity separates developmental and housekeeping gene regulation

机译：增强子-核心-启动子特异性将发育和管家基因调控分开

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摘要

Gene transcription in animals involves the assembly of RNA polymerase Ⅱ at core promoters and its cell-type-specific activation by enhancers that can be located more distally. However, how ubiquitous expression of housekeeping genes is achieved has been less clear. In particular, it is unknown whether ubiquitously active enhancers exist and how developmental and housekeeping gene regulation is separated. An attractive hypothesis is that different core promoters might exhibit an intrinsic specificity to certain enhancers. This is conceivable, as various core promoter sequence elements are differentially distributed between genes of different functions, including elements that are predominantly found at either develop-mentally regulated or at housekeeping genes. Here we show that thousands of enhancers in Drosophila melanogasterS2 and ovarian somatic cells (OSCs) exhibit a marked specificity to one of two core promoters-one derived from a ubiquitously expressed ribosomal protein gene and another from a developmentally regulated transcription factor-and confirm the existence of these two classes for five additional core promoters from genes with diverse functions. Housekeeping enhancers are active across the two cell types, while developmental enhancers exhibit strong cell-type specificity. Both enhancer classes differ in their genomic distribution, the functions of neighbouring genes, and the core promoter elements of these neighbouring genes. In addition, we identify two transcription factors-Dref and Trl-that bind and activate housekeeping versus developmental enhancers, respectively. Our results provide evidence for a sequence-encoded enhancer-core-promoter specificity that separates developmental and housekeeping gene regulatory programs for thousands of enhancers and their target genes across the entire genome.
机译：动物的基因转录涉及在核心启动子处的RNA聚合酶Ⅱ的组装及其在细胞末端的增强子对细胞类型的特异性激活。然而，如何获得管家基因的普遍表达还不清楚。特别是，尚不清楚是否普遍存在活性增强子，以及如何分离发育和管家基因调控。一个有吸引力的假设是，不同的核心启动子可能对某些增强子表现出固有的特异性。这是可以想象的，因为各种核心启动子序列元件在具有不同功能的基因之间差异分布，包括主要在发育调节的基因或管家基因中发现的元件。在这里，我们显示果蝇S2和卵巢体细胞（OSC）中成千上万的增强子对两个核心启动子之一显示出显着的特异性-一个核心启动子来自一个普遍存在的核糖体蛋白基因，另一个来自发育调控的转录因子-并确认存在这两个类别中有五个是来自具有不同功能的基因的另外五个核心启动子。管家增强剂在两种细胞类型中均具有活性，而发育增强剂则具有很强的细胞类型特异性。两种增强子类别的基因组分布，邻近基因的功能以及这些邻近基因的核心启动子元件均不同。此外，我们确定两个转录因子-Dref和Tr1-分别结合并激活管家与发育增强子。我们的结果为序列编码的增强子核心启动子特异性提供了证据，该特异性将整个基因组中成千上万个增强子及其靶基因的发育和管家基因调节程序分开。

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  • 来源
    《Nature》 |2015年第7540期|556-559|共4页
  • 作者

    Muhammad A. Zabidi; Cosmas D. Arnold; Katharina Schernhuber; Michaela Pagani; Martina Rath; Olga Frank; Alexander Stark;

  • 作者单位

    Research Institute of Molecular Pathology IMP, Vienna Biocenter VBC, Bohr-Gasse 7, 1030 Vienna, Austria;

    Research Institute of Molecular Pathology IMP, Vienna Biocenter VBC, Bohr-Gasse 7, 1030 Vienna, Austria;

    Research Institute of Molecular Pathology IMP, Vienna Biocenter VBC, Bohr-Gasse 7, 1030 Vienna, Austria;

    Research Institute of Molecular Pathology IMP, Vienna Biocenter VBC, Bohr-Gasse 7, 1030 Vienna, Austria;

    Research Institute of Molecular Pathology IMP, Vienna Biocenter VBC, Bohr-Gasse 7, 1030 Vienna, Austria;

    Research Institute of Molecular Pathology IMP, Vienna Biocenter VBC, Bohr-Gasse 7, 1030 Vienna, Austria;

    Research Institute of Molecular Pathology IMP, Vienna Biocenter VBC, Bohr-Gasse 7, 1030 Vienna, Austria;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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