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PionX sites mark the X chromosome for dosage compensation

机译：PionX位点标记X染色体以进行剂量补偿

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摘要

The rules defining which small fraction of related DNA sequences can be selectively bound by a transcription factor are poorly understood. One of the most challenging tasks in DNA recognition is posed by dosage compensation systems that require the distinction between sex chromosomes and autosomes. In Drosophila melanogaster, the male-specific lethal dosage compensation complex (MSL-DCC) doubles the level of transcription from the single male X chromosome, but the nature of this selectivity is not known(1). Previous efforts to identify X-chromosome-specific target sequences were unsuccessful as the identified MSL recognition elements lacked discriminative power(2,3). Therefore, additional determinants such as co-factors, chromatin features, RNA and chromosome conformation have been proposed to refine targeting further(4). Here, using an in vitro genome-wide DNA binding assay, we show that recognition of the X chromosome is an intrinsic feature of the MSL-DCC. MSL2, the male-specific organizer of the complex, uses two distinct DNA interaction surfaces-the CXC and proline/basic-residue-rich domains-to identify complex DNA elements on the X chromosome. Specificity is provided by the CXC domain, which binds a novel motif defined by DNA sequence and shape. This motif characterizes a subclass of MSL2-binding sites, which we name PionX (pioneering sites on the X) as they appeared early during the recent evolution of an X chromosome in D. miranda and are the first chromosomal sites to be bound during de novo MSL-DCC assembly. Our data provide the first, to our knowledge, documented molecular mechanism through which the dosage compensation machinery distinguishes the X chromosome from an autosome. They highlight fundamental principles in the recognition of complex DNA elements by protein that will have a strong impact on many aspects of chromosome biology.
机译：定义哪些小部分相关DNA序列可以被转录因子选择性结合的规则了解得很少。 DNA识别中最具挑战性的任务之一是剂量补偿系统提出的要求，该系统需要区分性染色体和常染色体。在果蝇中，雄性特异性致死剂量补偿复合物（MSL-DCC）使单个雄性X染色体的转录水平翻倍，但这种选择性的性质尚不清楚（1）。由于鉴定出的MSL识别元件缺乏判别力，因此先前鉴定X染色体特异性靶序列的努力未能成功（2,3）。因此，已经提出了其他决定因素，例如辅因子，染色质特征，RNA和染色体构象，以进一步完善靶向性（4）。在这里，使用体外全基因组DNA结合测定，我们表明X染色体的识别是MSL-DCC的固有特征。复合物的男性特异性组织者MSL2使用两个不同的DNA相互作用表面-CXC和富含脯氨酸/碱性残基的结构域-来识别X染色体上的复杂DNA元素。 CXC结构域提供了特异性，该结构域结合了由DNA序列和形状定义的新型基序。该基序表征了MSL2结合位点的一个亚类，我们将其命名为PionX（X上的开拓位点），因为它们是在米兰达D. miranda的X染色体最近进化期间早期出现的，并且是从头开始结合的第一个染色体位点MSL-DCC组件。就我们所知，我们的数据提供了第一个有据可查的分子机制，剂量补偿机制可通过该分子机制将X染色体与常染色体区分开。它们突出了蛋白质识别复杂DNA元素的基本原理，这将对染色体生物学的许多方面产生重大影响。

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  • 来源
    《Nature》 |2016年第7619期|244-248|共5页
  • 作者

    Villa Raffaella; Schauer Tamas; Smialowski Pawel; Straub Tobias; Becker Peter B.;

  • 作者单位

    Univ Munich, Div Mol Biol, Biomed Ctr, D-82152 Planegg Martinsried, Germany|Univ Munich, Ctr Integrated Prot Sci Munich, D-82152 Planegg Martinsried, Germany;

    Univ Munich, Div Mol Biol, Biomed Ctr, D-82152 Planegg Martinsried, Germany|Univ Munich, Ctr Integrated Prot Sci Munich, D-82152 Planegg Martinsried, Germany;

    Univ Munich, Bioinformat Unit, Biomed Ctr, D-82152 Planegg Martinsried, Germany;

    Univ Munich, Bioinformat Unit, Biomed Ctr, D-82152 Planegg Martinsried, Germany;

    Univ Munich, Div Mol Biol, Biomed Ctr, D-82152 Planegg Martinsried, Germany|Univ Munich, Ctr Integrated Prot Sci Munich, D-82152 Planegg Martinsried, Germany;

  • 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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