Dosage regulation of the active X chromosome in human triploid cells

Xinxian Deng, Di Kim Nguyen, R. Scott Hansen, Daniel L. Van Dyke, Stanley M. Gartler, Christine M. Disteche

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 Xlinked 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 similar in triploid versus diploid cells, indicating no apparent global effect on autosomal expression. In triploid cells with two active X's our data support a basic doubling of X-linked gene expression. However, in triploid cells with a single active X, X-linked gene expression is adjusted upward presumably by an epigenetic mechanism that senses the ratio between the number of active X chromosomes and autosomal sets. Such a mechanism may act on a subset of genes whose expression dosage in relation to autosomal expression may be critical. Indeed, we found that there was a range of individual X-linked gene expression in relation to ploidy and that a small subset (∼7%) of genes had expression levels apparently proportional to the number of autosomal sets.

Original languageEnglish (US)
Article numbere1000751
JournalPLoS Genetics
Volume5
Issue number12
DOIs
StatePublished - Dec 2009

Fingerprint

Chromosomes, Human, X
Triploidy
X chromosome
triploidy
gene expression
chromosome
X-Linked Genes
Gene Expression
dosage
cells
ploidy
Ploidies
autosomes
X Chromosome
Diploidy
Epigenomics
epigenetics
diploidy
sex linkage
gene

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Deng, X., Nguyen, D. K., Hansen, R. S., Van Dyke, D. L., Gartler, S. M., & Disteche, C. M. (2009). Dosage regulation of the active X chromosome in human triploid cells. PLoS Genetics, 5(12), [e1000751]. https://doi.org/10.1371/journal.pgen.1000751

Dosage regulation of the active X chromosome in human triploid cells. / Deng, Xinxian; Nguyen, Di Kim; Hansen, R. Scott; Van Dyke, Daniel L.; Gartler, Stanley M.; Disteche, Christine M.

In: PLoS Genetics, Vol. 5, No. 12, e1000751, 12.2009.

Research output: Contribution to journalArticle

Deng, X, Nguyen, DK, Hansen, RS, Van Dyke, DL, Gartler, SM & Disteche, CM 2009, 'Dosage regulation of the active X chromosome in human triploid cells', PLoS Genetics, vol. 5, no. 12, e1000751. https://doi.org/10.1371/journal.pgen.1000751
Deng X, Nguyen DK, Hansen RS, Van Dyke DL, Gartler SM, Disteche CM. Dosage regulation of the active X chromosome in human triploid cells. PLoS Genetics. 2009 Dec;5(12). e1000751. https://doi.org/10.1371/journal.pgen.1000751
Deng, Xinxian ; Nguyen, Di Kim ; Hansen, R. Scott ; Van Dyke, Daniel L. ; Gartler, Stanley M. ; Disteche, Christine M. / Dosage regulation of the active X chromosome in human triploid cells. In: PLoS Genetics. 2009 ; Vol. 5, No. 12.
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