Histone gene deficiencies and position–effect variegation in Drosophila

Abstract

Position–effect variegation, originally observed in insects, has since been demonstrated in plants and mammals. When cells bear a chromosomal rearrangement which juxtaposes a euchromatic gene near to heterochromatin, a fraction of the cells exhibit no expression of that gene. The resultant organism is a mosaic for activity of the rearranged gene. The degree of mosaicism can be modified; such factors as elevated developmental temperature, additional Y chromosome heterochromatin in the genome, and various modifier genes enhance the proportion of cells in which the gene is active¹. Although the phenomenon has been extensively documented, the underlying molecular mechanism of position–effect variegation remains unclear. The proportion of cells exhibiting gene inactivation increases with greater proximity of the rearranged gene locus to heterochromatin. It has been proposed that the variegating gene is inactivated by a ‘spreading effect’, or limited spatial diffusion of molecules from the adjacent heterochromatin². This explanation supposes that the juxtaposed gene locus is condensed into a transcriptionally inactive state, possibly by a phosphorylated histone protein subspecies characteristic of Drosophila heterochromatin³. Such a model leads to the prediction that an alteration in the amount of cellular histone protein would affect the expression of variegating genes. To test this prediction, we have investigated the effect of a reduction in the number of genes coding for histone protein on the degree of mosaicism observed in two variegating gene systems. Our results suggest that the amount of variegating gene expression is a function of histone gene multiplicity.