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首页> 外文期刊>Nature >Clustered DNA motifs mark X chromosomes for repression by a dosage compensation complex
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Clustered DNA motifs mark X chromosomes for repression by a dosage compensation complex

机译：簇状的DNA基序标记X染色体以通过剂量补偿复合物进行抑制

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Gene expression in metazoans is regulated not only at the level of individual genes but also in a coordinated manner across large chromosomal domains ( for example centromeres, telomeres and imprinted gene clusters(1-3)) and along entire chromosomes ( for example X-chromosome dosage compensation(4-6)). The primary DNA sequence usually specifies the regulation of individual genes, but the nature of cis-acting information that controls genes over large regions has been elusive: higher-order DNA structure, specific histone modifications, subnuclear compartmentalization and primary DNA sequence are possibilities. One paradigm of chromosome-wide gene regulation is Caenorhabditis elegans dosage compensation in which a large dosage compensation complex (DCC) is targeted to both X chromosomes of hermaphrodites to repress transcript levels by half(6). This essential process equalizes X-linked gene expression between the sexes (XO males and XX hermaphrodites). Here we report the discovery and dissection of cis-acting sites that mark nematode X chromosomes as targets for gene repression by the DCC. These rex ( recruitment element on X) sites are widely dispersed along X and reside in promoters, exons and intergenic regions. rex sites share at least two distinct motifs that act in combination to recruit the DCC. Mutating these motifs severely reduces or abolishes DCC binding in vivo, demonstrating the importance of primary DNA sequence in chromosome-wide regulation. Unexpectedly, the motifs are not enriched on X, but altering motif numbers within rex sites demonstrates that motif co-occurrence in unusually high densities is essential for optimal DCC recruitment. Thus, X-specific repression is established through sequences not specific to X. The distribution of common motifs provides the foundation for repression along an entire chromosome.
机译：后生动物中的基因表达不仅在单个基因的水平上受到调节，而且在整个染色体域（例如着丝粒，端粒和印迹基因簇（1-3））以及整个染色体（例如X染色体）上也以协调的方式受到调节。剂量补偿（4-6））。初级DNA序列通常指定单个基因的调控，但是控制大区域基因的顺式作用信息的性质难以捉摸：更高阶的DNA结构，特定的组蛋白修饰，亚核区室化和初级DNA序列是可能的。秀丽隐杆线虫的剂量补偿是染色体范围内基因调控的一个范例，其中大剂量补偿复合物（DCC）靶向于雌雄同体的两个X染色体，以将转录水平抑制一半（6）。这个必不可少的过程使性别（XO男性和XX雌雄同体）之间的X连锁基因表达相等。在这里我们报告发现和解剖标记线虫X染色体作为DCC基因抑制目标的顺式作用位点。这些rex（X上的募集元素）位点沿X广泛分布，并位于启动子，外显子和基因间区域。 rex位点共享至少两个不同的图案，这些图案组合起来以募集DCC。对这些基序进行突变会严重降低或消除体内DCC的结合，这表明一级DNA序列在整个染色体调控中的重要性。出乎意料的是，这些基序并没有在X上富集，但是rex位点内基序数的改变表明，异常高密度的基序共现对于最佳DCC募集至关重要。因此，通过非X特异的序列来建立X特异的抑制。常见基序的分布为沿着整个染色体的抑制提供了基础。

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