X chromosome dosage compensation proven in germ cells

X chromosome dosage compensation does occur in germ cells. A study published today in the open access journal Journal of Biology reveals that expression of the genes on the X chromosome is doubled in Drosophila germ cells to compensate for the missing second X chromosome. The study shows that this also occurs in C. elegans and mice somatic cells. In human female somatic cells, one of the two X chromosomes is inactivated to equilibrate expression between the sexes, but this unbalances the expression of the X compared to the other chromosomes. This study is the first demonstration that the X chromosome is upregulated in germs cells, which brings the X chromosome and the other chromosomes back into balance. The study is also the first demonstration that upregulation of the X chromosome in somatic tissue is conserved across species.

Vaijayanti Gupta from the National Institute of Diabetes and Digestive and Kidney Disease at the National Institutes of Health (NIH), Bethesda, USA collaborated with colleagues from the Center for Information Technology at the NIH and colleagues from Incyte Genomics, Palo Alto, USA. Gupta et al. carried out microarray analyses of 2,245 genes present on the X chromosome of Drosophila germ cells and somatic cells. Drosophila males have one X chromosome and two autosomes (X;AA) while Drosophila females have two X chromosomes and two autosomes (XX;AA).

The results of the microarray analyses show that the single male X chromosome is expressed at the same level as the two female X chromosomes put together in both somatic cells and germ cells. By creating sex-transformed flies, Gupta et al. were able to show a two-fold X-chromosome mRNA level difference compared with the autosomes in both male and female germ cells with a single X chromosome. This indicates that the X chromosome is hypertranscribed compared to the autosomes in germ cells. Gupta et al.'s results suggest that the two X chromosomes in female germ cells are repressed to match their expression to the autosomes. The authors also demonstrate that dosage compensation occurs for all the genes on the X chromosome.

Gupta et al. then show that dosage compensation by increased X chromosome expression occurs in male and female somatic cells in C.elegans and mice, and suggest that dosage compensation is essential across species.

In Drosophila somatic cells, dosage compensation is dependent on the male-specific-lethal complex - a set of acetylating proteins and non-coding RNAs that increase gene expression. This complex is not present in germ cells and the authors write "there are a host of post transcriptional mechanisms that could conceivably mediate germline dosage compensation."

Article:
Global analysis of X-Chromosome dosage compensation
Vaijayanti Gupta, Michael Parisi, David Sturgill, Rachel Nuttall, Michael Doctolero, James Malley, Olgoa Dudko, P Scott Eastman, Brian Oliver
Journal of Biology 2006, 5:3 (16 February 2006)

This article is accompanied by a Research News article and a Minireview

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