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

• Type of Material: Article
• Authors: Leila Rieder, Emory University; William Thomas Jordan III, Brown University; Erica Nicole Larschan, Brown University
• Language: English
• Date: 2019-12-24
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 The Authors
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.celrep.2019.11.095
• Title of Journal or Parent Work: Cell Reports
• Volume: 29
• Issue: 13
• Start Page: 4268
• End Page: 4275.e2
• Grant/Funding Information: This work was supported by NIH F32GM109663, K99HD092625, and R00HD092625 to L.E.R.; NIH R35GM126994 to E.N.L.; and a HHMI Gilliam fellowship and a NSF GRFP grant to W.T.J.
• Keywords: Gene Expression Regulation, Developmental; meiotic drive; Segregation distorter; Chromatin; Reproducibility of Results; transcription factor; X Chromosome; Drosophila melanogaster; chromatin domain; Meiosis; MSL complex; Embryo, Nonmammalian; Male; zygotic genome activation; dosage compensation; Embryonic Development; Female; CLAMP; Drosophila; Animals; Drosophila Proteins; Dosage Compensation, Genetic
• Research Categories: Biology, Genetics; Biology, Molecular; Chemistry, Biochemistry; Health Sciences, Human Development

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.