Targeting of the Dosage-Compensated Male X-Chromosome during Early Drosophila Development

Abstract

Summary: Dosage compensation, which corrects for the imbalance in X-linked gene expression between XX females and XY males, represents a model for how genes are targeted for coordinated regulation. However, the mechanism by which dosage compensation complexes identify the X chromosome during early development remains unknown because of the difficulty of sexing embryos before zygotic transcription using X- or Y-linked reporter transgenes. We used meiotic drive to sex Drosophila embryos before zygotic transcription and ChIP-seq to measure the dynamics of dosage compensation factor targeting. The Drosophila male-specific lethal dosage compensation complex (MSLc) requires the ubiquitous zinc-finger protein chromatin-linked adaptor for MSL proteins (CLAMP) to identify the X chromosome. We observe a multi-stage process in which MSLc first identifies CLAMP binding sites throughout the genome, followed by concentration at the strongest X-linked MSLc sites. We provide insight into the dynamics of binding site recognition by a large transcription complex during early development. : Rieder et al. establish a meiotic drive system to study Drosophila X chromosome dosage compensation before the maternal-zygotic transition. This study uncovers another step in the process during which the dosage compensation complex identifies binding sites genome-wide before becoming enriched on the X chromosome. Keywords: dosage compensation, transcription factor, zygotic genome activation, meiotic drive, chromatin domain, CLAMP, MSL complex, Drosophila, Segregation distorter, dosage compensation