Principles and mechanisms of X chromosome recognition during dosage compensation in Drosophila

果蝇X染色体剂量补偿的过程包括将雄性果蝇中单个X染色体的转录加倍，以匹配雌性果蝇中两个X染色体的组合输出。转录是由“剂量补偿复合物”（DCC）激活的，DCC是一种含有五种蛋白质和非编码roX RNA的未知结构的组装体。的原则，让DCC歧视染色体和相互作用的X与精致exclusivity.Enhancing最近描述的第一个X特异性DNA签名，我们设计了一个实验策略，以确定X染色体靶向元件监控DCC在体外的选择性相互作用。我们建议的一个中心方面是将整个果蝇基因组组装成复杂的生理染色质，即DCC相互作用的天然底物。破译X染色体同一性的原则将结束对神秘的X染色体决定簇的探索，该决定簇激发了该领域几十年的灵感，并将揭示新的和一般的规则，通过这些规则解释复杂的DNA签名，并揭示赋予靶向系统鲁棒性的合作相互作用的性质。

The process of X chromosome dosage compensation in Drosophila involves doubling the transcription from the single X in male flies to match the combined output of the two X chromosomes in female flies. Transcription is activated by the "Dosage Compensation Complex" (DCC), an assembly of unknown structure containing five proteins and non-coding roX RNA.The transcriptional tuning must be restricted to the X, or male viability is seriously compromised. The principles that allow the DCC to discriminate chromosomes and to interact with the X with exquisite exclusivity are still elusive.Encouraged by our recent description of a first X-specific DNA signature we devised an experimental strategy to identify X-chromosomal targeting elements monitoring the selective interactions of the DCC in vitro. A central aspect of our proposal is to assemble the entire Drosophila genome into complex, physiological chromatin, the natural substrate for DCC interactions. Deciphering the principles of X chromosome identity will end the quest for the mysterious X chromosomal determinant that inspired the field for decades, and will uncover new and general rules through which complex DNA signatures are interpreted and reveal the nature of the cooperative interactions that endow targeting systems with robustness.