X chromosome repression by localization of the C-elegans dosage compensation machinery to sites of transcription initiation
X chromosome repression by localization of the C-elegans dosage compensation machinery to sites of transcription initiation
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DOI：
10.1038/ng1983
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发表时间：
2007-03-01
期刊：
影响因子：
30.8
通讯作者：
Lieb, Jason D.
中科院分区：
文献类型：
--
作者：
Ercan, Sevinc;Giresi, Paul G.;Lieb, Jason D.
在具有基于染色体的性别决定机制的生物中，两性之间X连锁基因表达不均衡通常是致命的。在秀丽隐杆线虫中，XX型雌雄同体将每条X染色体的转录减半，以匹配XO型雄性的输出量。在此，我们绘制了凝聚蛋白同源物DPY - 27和锌指蛋白SDC - 3（秀丽隐杆线虫剂量补偿复合物（DCC）的两个组分）的结合位置。我们观察到DCC在X染色体上有强烈的结合焦点，周围是更广泛的定位区域。结合焦点（而非相邻的定位区域）可通过一个10bp的DNA基序簇来区分，这表明存在一种X染色体识别的招募 - 扩散机制。DCC优先结合在基因的上游，这表明其对转录起始和聚合酶偶联扩散的调节作用。在具有高转录活性的基因上游，DCC结合更强，这表明存在一种在特定位点调节DCC活性的机制。这些数据有助于理解参与高阶染色体动力学的蛋白质如何调控单个基因座的转录。
Among organisms with chromosome-based mechanisms of sex determination, failure to equalize expression of X-linked genes between the sexes is typically lethal. In C. elegans, XX hermaphrodites halve transcription from each X chromosome to match the output of XO males(1). Here, we mapped the binding location of the condensin homolog DPY-27 and the zinc finger protein SDC-3, two components of the C. elegans dosage compensation complex (DCC)(2,3). We observed strong foci of DCC binding on X, surrounded by broader regions of localization. Binding foci, but not adjacent regions of localization, were distinguished by clusters of a 10-bp DNA motif, suggesting a recruitment-and-spreading mechanism for X recognition. The DCC was preferentially bound upstream of genes, suggesting modulation of transcriptional initiation and polymerase-coupled spreading. Stronger DCC binding upstream of genes with high transcriptional activity indicated a mechanism for tuning DCC activity at specific loci. These data aid in understanding how proteins involved in higherorder chromosome dynamics can regulate transcription at individual loci.