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

Cell Rep. 2019 Dec 24;29(13):4268-4275.e2. doi: 10.1016/j.celrep.2019.11.095.

Abstract

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.

Keywords: CLAMP; Drosophila; MSL complex; Segregation distorter; chromatin domain; dosage compensation; meiotic drive; transcription factor; zygotic genome activation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Chromatin / metabolism
  • Dosage Compensation, Genetic*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / embryology*
  • Drosophila melanogaster / genetics*
  • Embryo, Nonmammalian / metabolism
  • Embryonic Development / genetics*
  • Female
  • Gene Expression Regulation, Developmental
  • Male
  • Meiosis / genetics
  • Reproducibility of Results
  • X Chromosome / genetics*

Substances

  • Chromatin
  • Drosophila Proteins