The dosage compensation complex (DCC) of Drosophila identifies its X-chromosomal binding sites with exquisite selectivity. The principles that assure this vital targeting are known from the D. melanogaster model: DCC-intrinsic specificity of DNA binding, cooperativity with the CLAMP protein, and noncoding roX2 RNA transcribed from the X chromosome. We found that in D. virilis, a species separated from melanogaster by 40 million years of evolution, all principles are active but contribute differently to X specificity. In melanogaster, the DCC subunit MSL2 evolved intrinsic DNA-binding selectivity for rare PionX sites, which mark the X chromosome. In virilis, PionX motifs are abundant and not X-enriched. Accordingly, MSL2 lacks specific recognition. Here, roX2 RNA plays a more instructive role, counteracting a nonproductive interaction of CLAMP and modulating DCC binding selectivity. Remarkably, roX2 triggers a stable chromatin binding mode characteristic of DCC. Evidently, X-specific regulation is achieved by divergent evolution of protein, DNA, and RNA components.

中文翻译：

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果蝇性染色体特异性基因调控的发散进化

果蝇的剂量补偿复合物 (DCC) 以极高的选择性识别其 X 染色体结合位点。确保这种重要靶向的原理从D. melanogaster模型中得知：DNA 结合的 DCC 固有特异性、与 CLAMP 蛋白的协同性以及从 X 染色体转录的非编码 roX2 RNA。我们发现，在D. virilis中，一个经过 4000 万年进化与黑腹果蝇分离的物种，所有原理都是活跃的，但对 X 特异性的贡献不同。在黑腹果蝇中，DCC 亚基 MSL2 进化出对稀有 PionX 位点（标记 X 染色体）的内在 DNA 结合选择性。在virilis, PionX 基序丰富且不富含 X。因此，MSL2 缺乏特异性识别。在这里，roX2 RNA 发挥了更具指导性的作用，抵消了 CLAMP 的非生产性相互作用并调节 DCC 结合选择性。值得注意的是，roX2 触发了 DCC 的稳定染色质结合模式特征。显然，X 特异性调节是通过蛋白质、DNA 和 RNA 成分的不同进化来实现的。