Drosophila dosage compensation is an important model system for defining how active chromatin domains are formed. The male-specific lethal dosage compensation complex (MSLc) increases transcript levels of genes along the length of the single male X-chromosome to equalize with that expressed from the two female X-chromosomes. The strongest binding sites for MSLc cluster together in three-dimensional space largely independent of MSLc because clustering occurs in both sexes. CLAMP, a non-sex specific, ubiquitous zinc finger protein, binds synergistically with MSLc to enrich the occupancy of both factors on the male X-chromosome. Here, we demonstrate that CLAMP promotes the observed three-dimensional clustering of MSLc binding sites. Moreover, the X-enriched CLAMP protein more strongly promotes longer-range three-dimensional interactions on the X-chromosome than autosomes. Genome-wide, CLAMP promotes three-dimensional interactions between active chromatin regions together with other insulator proteins. Overall, we define how long-range interactions which are modulated by a locally enriched ubiquitous transcription factor promote hyper-activation of the X-chromosome to mediate dosage compensation.

中文翻译：

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锌指蛋白 CLAMP 促进长程染色质相互作用，介导果蝇雄性 X 染色体的剂量补偿

果蝇剂量补偿是定义活性染色质结构域如何形成的重要模型系统。雄性特异性致死剂量补偿复合物 (MSLc) 增加了沿单个雄性 X 染色体长度的基因转录水平，以使其与两条雌性 X 染色体表达的水平相等。MSLc 的最强结合位点在很大程度上独立于 MSLc 的三维空间中聚集在一起，因为聚集发生在两性中。CLAMP 是一种非性别特异性、普遍存在的锌指蛋白，它与 MSLc 协同结合，以丰富这两种因子在男性 X 染色体上的占有率。在这里，我们证明 CLAMP 促进了观察到的 MSLc 结合位点的三维聚类。而且，与常染色体相比，富含 X 的 CLAMP 蛋白更强烈地促进 X 染色体上更远距离的三维相互作用。在全基因组范围内，CLAMP 促进活性染色质区域与其他绝缘体蛋白之间的三维相互作用。总体而言，我们定义了由局部富集的普遍转录因子调节的远程相互作用如何促进 X 染色体的过度激活以介导剂量补偿。