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

• Applicant: Professor Dr. Peter Burkhard Becker
• Subject Area: General Genetics and Functional Genome Biology
• Term: from 2016 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 319248348

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.

• DFG Programme: Reinhart Koselleck Projects