Abstract
Monosomy of the X chromosome owing to divergence between the sex chromosomes leads to dosage compensation mechanisms to restore balanced expression between the X and the autosomes. In Drosophila melanogaster, upregulation of the male X leads to dosage compensation. It has been hypothesized that mammals likewise upregulate their active X chromosome. Together with X inactivation, this mechanism would maintain balanced expression between the X chromosome and autosomes and between the sexes. Here, we show that doubling of the global expression level of the X chromosome leads to dosage compensation in somatic tissues from several mammalian species. X-linked genes are highly expressed in brain tissues, consistent with a role in cognitive functions. Furthermore, the X chromosome is expressed but not upregulated in spermatids and secondary oocytes, preserving balanced expression of the genome in these haploid cells. Upon fertilization, upregulation of the active X must occur to achieve the observed dosage compensation in early embryos.
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Acknowledgements
This work was supported by grants from the US National Institutes of Health (NIH). We thank J. Birchler (University of Missouri), B. Oliver (National Institute of Diabetes & Digestive & Kidney Diseases, NIH) and M. Cheng (University of Washington), for helpful discussions. We thank C. Pritchard, I. Coleman and P. Nelson (Fred Hutchinson Cancer Research Center); J. Hogenesch, T. Wilshire and J. Walker (Genomics Institute of the Novartis Research Foundation); G. Martin and B. Cool (Department of Pathology, University of Washington); C. Bondy (National Institute of Child Health, NIH); M. Ko (National Institute of Aging, NIH); P. Khaitovich (Max-Planck-Institute for Evolutionary Anthropology, Leipzig); R. Bumgarner and the staff at Array Expression Database (http://www.ebi.ac.uk/arrayexpress/) for providing data for these analyses. We thank the Locke Computer Center and the Department of Biostatistics (University of Washington) for help with the statistical analysis, L. McKitrick and H. Vendettuoli, for technical assistance.
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Supplementary information
Supplementary Fig. 1
Repression of the X chromosome during testis development. (PDF 275 kb)
Supplementary Table 1
Array types and characteristics. (PDF 60 kb)
Supplementary Table 2
X:autosome expression ratios. (PDF 41 kb)
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Nguyen, D., Disteche, C. Dosage compensation of the active X chromosome in mammals. Nat Genet 38, 47–53 (2006). https://doi.org/10.1038/ng1705
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DOI: https://doi.org/10.1038/ng1705
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