Evidence for compensatory upregulation of expressed X-linked genes in mammals, Caenorhabditis elegans and Drosophila melanogaster

Xinxian Deng, Joseph B. Hiatt, Di Kim Nguyen, Sevinc Ercan, David Sturgill, Ladeana W. Hillier, Felix Schlesinger, Carrie A. Davis, Valerie J. Reinke, Thomas R. Gingeras, Jay Shendure, Robert H. Waterston, Brian Oliver, Jason D. Lieb, Christine M. Disteche

Research output: Contribution to journalArticle

Abstract

Many animal species use a chromosome-based mechanism of sex determination, which has led to the coordinate evolution of dosage-compensation systems. Dosage compensation not only corrects the imbalance in the number of X chromosomes between the sexes but also is hypothesized to correct dosage imbalance within cells that is due to monoallelic X-linked expression and biallelic autosomal expression, by upregulating X-linked genes twofold (termed 'Ohno's hypothesis'). Although this hypothesis is well supported by expression analyses of individual X-linked genes and by microarray-based transcriptome analyses, it was challenged by a recent study using RNA sequencing and proteomics. We obtained new, independent RNA-seq data, measured RNA polymerase distribution and reanalyzed published expression data in mammals, C. elegans and Drosophila. Our analyses, which take into account the skewed gene content of the X chromosome, support the hypothesis of upregulation of expressed X-linked genes to balance expression of the genome.

Original languageEnglish (US)
Pages (from-to)1179-1185
Number of pages7
JournalNature Genetics
Volume43
Issue number12
DOIs
StatePublished - Dec 2011

ASJC Scopus subject areas

  • Genetics

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    Deng, X., Hiatt, J. B., Nguyen, D. K., Ercan, S., Sturgill, D., Hillier, L. W., Schlesinger, F., Davis, C. A., Reinke, V. J., Gingeras, T. R., Shendure, J., Waterston, R. H., Oliver, B., Lieb, J. D., & Disteche, C. M. (2011). Evidence for compensatory upregulation of expressed X-linked genes in mammals, Caenorhabditis elegans and Drosophila melanogaster. Nature Genetics, 43(12), 1179-1185. https://doi.org/10.1038/ng.948