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

果蝇的X染色体剂量补偿过程包括雄性果蝇中单个X染色体的转录翻倍，以匹配雌性果蝇中两条X染色体的组合输出。转录是由“剂量补偿复合体”(DCC)激活的，DCC是一种含有5种蛋白质和非编码Rox RNA的未知结构的组装。转录调节必须限于X，否则男性的生存能力会受到严重影响。允许DCC区分染色体并与X以精致的排他性相互作用的原则仍然难以捉摸。受我们最近描述的第一个X特异DNA签名的鼓舞，我们设计了一种实验策略来识别X染色体靶向元件，监测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、生理的染色质，这是DCC相互作用的自然底物。破译X染色体识别的原理将结束对激励该领域数十年的神秘X染色体决定因素的探索，并将揭示新的一般规则，通过这些规则解释复杂的DNA签名，并揭示赋予靶向系统稳健性的合作相互作用的本质。

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.