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.
Birchler
James A
JA
University of Missouri, Columbia, 117 Tucker Hall, Columbia, MO 65211-7400, USA. BirchlerJ@Missouri.edu
Pal-Bhadra
Manika
M
Bhadra
Utpal
U
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