The essential process of dosage compensation, which corrects for the imbalance in Xlinked gene expression between XX females and XY males, represents a key model for how genes are targeted for coordinated regulation. However, the mechanism by which dosage compensation complexes identify the Xchromosome during early development remained unknown because of the difficulty of sexing embryos prior to zygotic transcription. We used meiotic drive to sex Drosophila embryos prior to zygotic transcription and ChIPseq to measure dynamics of dosage compensation factor targeting. The Drosophila MaleSpecific Lethal dosage compensation complex (MSLc) requires the ubiquitous zincfinger protein ChromatinLinked Adaptor for MSL Proteins (CLAMP) to identify the Xchromosome. We observe a multistage process in which MSLc first identifies CLAMP binding sites throughout the genome followed by concentration at the strongest Xlinked MSLc sites. We provide insight into the dynamic mechanism by which a large transcription complex identifies its binding sites during early development.

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