Dosage compensation of the active X chromosome in mammals.
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.
Nguyen
Di Kim
DK
Department of Pathology, University of Washington, Seattle, Washington 98195, USA.
Disteche
Christine M
CM
D000818:Animals; D001921:Brain / Q000502:physiology; D004303:Dosage Compensation, Genetic; D004330:Drosophila / Q000235:genetics; D047108:Embryonic Development / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008297:Male; D008322:Mammals / Q000235:genetics*; D051379:Mice; D009865:Oocytes / Q000502:physiology; D013087:Spermatids / Q000502:physiology; D015854:Up-Regulation; D014960:X Chromosome / Q000235:genetics*; D049951:X Chromosome Inactivation