Dosage Compensation In The Mouse Balances Up-Regulation And Silencing Of X-Linked Genes

Main Category: Biology / Biochemistry
Article Date: 10 Dec 2007 - 17:00 PDT

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In organisms such as fruit flies and humans, major chromosomal differences exist between the sexes: females have two large, gene-rich X chromosomes and males have one X and one small, gene-poor Y.

Various strategies have evolved to balance X-linked gene expression both between the single X and the autosomes, and between the sexes (a phenomenon called dosage compensation). In Drosophila melanogaster, to equalize expression from the X chromosomes in males and females, expression from the male X is up-regulated approximately two-fold to compensate for the fact that females have two X chromosomes. In contrast, mammals achieve dosage compensation by silencing one of the two female X chromosomes; the untranslated RNA product of the Xist gene mediates inactivation of the X chromosome.

Published this week in the online open-access journal PLoS Biology, Hong Lin, Laura O'Neill, Bryan Turner, and colleagues show that by using mouse embryonic stem (ES) cells and microarray expression analysis, the dosage compensation in mice is more complex than previously thought, with clear up-regulation of X-linked genes in both male and female cells so as to maintain a balance of X to autosome expression.

As differentiation proceeds, female cells show progressive loss of expression from one of the two initially active Xs. Surprisingly, silencing occurs on a gene-by-gene basis over 2-3 weeks of differentiation; some genes escape altogether while a sub-group of genes, often adjacent to the Xist locus, are silenced even in undifferentiated cells. They propose that female X-linked genes are silenced by progressive spreading of Xist RNA through the X chromosome territory as differentiation proceeds.

Citation: Lin H, Gupta V, VerMilyea MD, Falciani F, Lee JT, et al. (2007) Dosage compensation in the mouse balances up-regulation and silencing of X-linked genes.
PLoS Biol 5(12): e326. doi:10.1371/journal.pbio.0050326
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