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Dosage Dependent Gene Regulation and the Compensation of the X Chromosome in Drosophila Males

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Abstract

Dosage compensation refers to the phenomenon that despite the difference in copy number of X chromosomes in males and females approximately equal expression results from the sex chromosomes. We describe evidence for a model that dosage compensation is caused by an 'inverse dosage effect’ that results from an altered stoichiometry of transcriptional regulators on the X versus the autosomes. This imbalance of regulators would cause a two-fold increase in target gene expression throughout the genome in the absence of any modification. The two-fold hyperactivation compensates the X chromosome. However, the MSL (male specific lethal) complex modifies this effect on the autosomes, which would otherwise double their expression, by becoming sequestered to the X chromosome together with a histone acetylase (MOF) and kinase (JIL1). This situation reduces the level of histone 4 Lys16 acetylation and H3 phosphorylation on the autosomes, thus bringing their expression down to near the female level. The presence of the MSL complex on the X modifies chromatin in such a manner that it counteracts any impact of increased histone acetylation and phosphorylation on gene expression. This situation fosters the proper two-fold increase in gene expression needed for X chromosomal dosage compensation in males and reduces the inverse effect on the autosomes to equalize gene expression throughout the genome for the two sexes.

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  1. Manika Pal-Bhadra & Utpal Bhadra

    Present address: Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, 500007, India

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  1. University of Missouri, Columbia, 117 Tucker Hall, Columbia, MO, 65211-7400, USA

    James A. Birchler, Manika Pal-Bhadra & Utpal Bhadra

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Birchler, J.A., Pal-Bhadra, M. & Bhadra, U. Dosage Dependent Gene Regulation and the Compensation of the X Chromosome in Drosophila Males. Genetica 117, 179–190 (2003). https://doi.org/10.1023/A:1022935927763

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