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Different but equal: Settling the dosage compensation debate

October 03, 2005

Independent research papers from Dr. Peter Becker (Munich, Germany) and Dr. Mitzi Kuroda (Boston, MA) in the October 1 issue of Genes & Development delineate the mechanism of X-chromosome dosage compensation in Drosophila.

In Drosophila, like in humans, male cells have a single X chromosome, while female cells have two. Researchers have long debated over how X and autosomal chromosome gene expression is equalized between the sexes (generally regarding two different models, known as the activation model and the inverse model). These two papers provide the first definitive in vivo evidence in favor of the activation model of dosage compensation in flies.

The male-specific-lethal (MSL) complex functions as a male-specific regulatory protein complex that controls gene expression in male fruit fly cells. The activation model proposes that MSL upregulates the transcription of X-linked genes twofold in male cells. The inverse dosage effect model proposes that MSL represses male autosomal gene expression to balance gene expression.

The Becker and Kuroda labs both utilized RNAi technology to analyze the effects of decreased MSL expression. Using different, yet complementary, experimental systems, both found that MSL downregulation results in reduced expression of most X-linked genes, while not affecting autosomal gene expression levels. These results clarify the role of MSL as a specific activator of X-linked gene expression, and that dosage compensation occurs by a twofold upregulation of the single X chromosome in male fly cells.

Dr. Becker states that "The clear-cut result we obtained clarifies this controversial issue at least to our satisfaction. How the different components of the male-specific lethal complex contribute to fine-tuning of gene expression in a two-fold range remains an interesting challenge for future studies."

Cold Spring Harbor Laboratory