dosage regulation of the active x chromosome in human triploid cells剂量调节活跃在人类三倍体染色体的细胞.pdfVIP

Dosage Regulation of the Active X Chromosome in Human Triploid Cells 1 1 2,3 4 2,3 Xinxian Deng , Di Kim Nguyen , R. Scott Hansen , Daniel L. Van Dyke , Stanley M. Gartler , Christine M. Disteche1,2* 1 Department of Pathology, University of Washington, Seattle, Washington, United States of America, 2 Department of Medicine, University of Washington, Seattle, Washington, United States of America, 3 Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America, 4 Mayo Clinic College of Medicine, Rochester, Minnesota, United States of America Abstract In mammals, dosage compensation is achieved by doubling expression of X-linked genes in both sexes, together with X inactivation in females. Up-regulation of the active X chromosome may be controlled by DNA sequence–based and/or epigenetic mechanisms that double the X output potentially in response to autosomal factor(s). To determine whether X expression is adjusted depending on ploidy, we used expression arrays to compare X-linked and autosomal gene expression in human triploid cells. While the average X:autosome expression ratio was about 1 in normal diploid cells, this ratio was lower (0.81–0.84) in triploid cells with one active X and higher (1.32–1.4) in triploid cells with two active X’s. Thus, overall X- linked gene expression in triploid cells does not strictly respond to an autosomal factor, nor is it adjusted to achieve a perfect balance. The unbalanced X:autosome expression ratios that we observed could contribute to the abnormal phenotypes associated with triploidy. Absolute autosomal expression levels per gene copy were s