Dosage dependent gene regulation and the compensation of the X chromosome in Drosophila males.
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.
University of Missouri, Columbia, 117 Tucker Hall, Columbia, MO 65211-7400, USA. BirchlerJ@Missouri.edu
James A
JA
Birchler
Manika
M
Pal-Bhadra
Utpal
U
Bhadra
D000123:Acetyltransferases / Q000235:genetics; D000818:Animals; D002843:Chromatin / Q000235:genetics; D004303:Dosage Compensation, Genetic; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins; D019143:Evolution, Molecular; D051548:Histone Acetyltransferases; D006657:Histones / Q000235:genetics; D008297:Male; D009687:Nuclear Proteins; D014158:Transcription, Genetic; D014960:X Chromosome / Q000235:genetics*
D002843:Chromatin; D029721:Drosophila Proteins; D006657:Histones; D009687:Nuclear Proteins; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C111063:mof protein, Drosophila