Nature Genetics 38, 47 - 53 (2006)
Published online: 11 December 2005; | doi:10.1038/ng1705
Dosage compensation of the active X chromosome in mammalsDi Kim Nguyen1
& Christine M Disteche1, 21
Department of Pathology, University of Washington, Seattle, Washington 98195, USA. 2
Department of Medicine, University of Washington, Seattle, Washington 98195, USA.
Correspondence should be addressed to Christine M Disteche cdistech@u.washington.edu 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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