Journal
NATURE GENETICS
Volume 43, Issue 12, Pages 1179-U28Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.948
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Funding
- US National Institutes of Health [GM079537]
- modENCODE [HG004270, HG004263, AG039173]
- ENCODE [HG004557]
- National Institute of Diabetes and Digestive and Kidney Diseases
- William H. Gates III Endowed Chair of Biomedical Sciences
- Achievement Rewards for College Scientists
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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.
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