title: Untangling the Contributions of Sex-Specific Gene Regulation and X-Chromosome Dosage to Sex-Biased Gene Expression in Caenorhabditis elegans.
abstract: Dosage compensation mechanisms equalize the level of X chromosome expression between sexes. Yet the X chromosome is often enriched for genes exhibiting sex-biased, i.e., imbalanced expression. The relationship between X chromosome dosage compensation and sex-biased gene expression remains largely unexplored. Most studies determine sex-biased gene expression without distinguishing between contributions from X chromosome copy number (dose) and the animal's sex. Here, we uncoupled X chromosome dose from sex-specific gene regulation in Caenorhabditis elegans to determine the effect of each on X expression. In early embryogenesis, when dosage compensation is not yet fully active, X chromosome dose drives the hermaphrodite-biased expression of many X-linked genes, including several genes that were shown to be responsible for hermaphrodite fate. A similar effect is seen in the C. elegans germline, where X chromosome dose contributes to higher hermaphrodite X expression, suggesting that lack of dosage compensation in the germline may have a role in supporting higher expression of X chromosomal genes with female-biased functions in the gonad. In the soma, dosage compensation effectively balances X expression between the sexes. As a result, somatic sex-biased expression is almost entirely due to sex-specific gene regulation. These results suggest that lack of dosage compensation in different tissues and developmental stages allow X chromosome copy number to contribute to sex-biased gene expression and function.
authors.affiliation: Department of Biology, Center for Genomics and Systems Biology, New York University, New York 10003.
authors.forename: Maxwell
authors.initials: M
authors.lastname: Kramer
authors.affiliation: Department of Biology, Center for Genomics and Systems Biology, New York University, New York 10003.
authors.forename: Prashant
authors.initials: P
authors.lastname: Rao
authors.affiliation: Department of Biology, Center for Genomics and Systems Biology, New York University, New York 10003 se71@nyu.edu.
authors.forename: Sevinc
authors.initials: S
authors.lastname: Ercan
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis / Q000235:genetics; D004303:Dosage Compensation, Genetic; D005260:Female; D018507:Gene Expression Regulation, Developmental; D050172:Genes, X-Linked; D008297:Male; D012737:Sex Factors; D014960:X Chromosome
chemical_list: D029742:Caenorhabditis elegans Proteins
keywords: C. elegans; RNA-seq; X chromosome; XO; chromatin; dosage compensation; gene regulation; genetics of sex; germline; sex; sex-biased gene expression; transcription