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Global analysis of X-chromosome dosage compensation

Vaijayanti Gupta1 email, Michael Parisi1 email, David Sturgill1 email, Rachel Nuttall2,4 email, Michael Doctolero2,4 email, Olga K Dudko3 email, James D Malley3 email, P Scott Eastman2,4 email and Brian Oliver1 email

Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 50 South Drive, Bethesda, MD 20892, USA

Incyte Genomics, Palo Alto, CA 94304, USA

Mathematical and Statistical Computing Laboratory, Division of Computational Bioscience, Center for Information Technology, National Institutes of Health, Bethesda, MD 20982, USA

Current address: Quantum Dot Corporation, Hayward, CA 94545, USA

author email corresponding author email

Journal of Biology 2006, 5:3doi:10.1186/jbiol30

Published: 16 February 2006

Abstract

Background

Drosophila melanogaster females have two X chromosomes and two autosome sets (XX;AA), while males have a single X chromosome and two autosome sets (X;AA). Drosophila male somatic cells compensate for a single copy of the X chromosome by deploying male-specific-lethal (MSL) complexes that increase transcription from the X chromosome. Male germ cells lack MSL complexes, indicating that either germline X-chromosome dosage compensation is MSL-independent, or that germ cells do not carry out dosage compensation.

Results

To investigate whether dosage compensation occurs in germ cells, we directly assayed X-chromosome transcripts using DNA microarrays and show equivalent expression in XX;AA and X;AA germline tissues. In X;AA germ cells, expression from the single X chromosome is about twice that of a single autosome. This mechanism ensures balanced X-chromosome expression between the sexes and, more importantly, it ensures balanced expression between the single X chromosome and the autosome set. Oddly, the inactivation of an X chromosome in mammalian females reduces the effective X-chromosome dose and means that females face the same X-chromosome transcript deficiency as males. Contrary to most current dosage-compensation models, we also show increased X-chromosome expression in X;AA and XX;AA somatic cells of Caenorhabditis elegans and mice.

Conclusion

Drosophila germ cells compensate for X-chromosome dose. This occurs by equilibrating X-chromosome and autosome expression in X;AA cells. Increased expression of the X chromosome in X;AA individuals appears to be phylogenetically conserved.


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