Genetics, Vol 131, 345-352, Copyright © 1992

INVESTIGATIONS

The Heterochromatin-Associated Protein HP-1 Is an Essential Protein in Drosophila With Dosage-Dependent Effects on Position-Effect Variegation

J. C. Eissenberg, G. D. Morris, G. Reuter and T. Hartnett
Edward A. Doisy Department of Biochemistry and Molecular Biology University School of Medicine, St. Louis, Missouri 63104

Chromosome rearrangements which place euchromatic genes adjacent to a heterochromatic break-point frequently result in gene repression (position-effect variegation). This repression is thought to reflect the spreading of a heterochromatic structure into neighboring euchromatin. Two allelic dominant suppressors of position-effect variegation were found to contain mutations within the gene encoding the heterochromatin-specific chromosomal protein HP-1. The site of mutation for each allele is given: one converts Lys(169) into a nonsense (ochre) codon, while the other is a frameshift after Ser(10). In flies heterozygous for one of the mutant alleles (Su(var)2-5(04)), a truncated HP-1 protein was detectable by Western blot analysis. An HP-1 minigene, consisting of HP-1 cDNA under the control of an Hsp70 heat-inducible promoter, was transduced into flies by P element-mediated germ line transformation. Heat-shock driven expression of this minigene results in elevated HP-1 protein level and enhancement of position-effect variegation. Levels of variegating gene expression thus appear to depend upon the level of expression of a heterochromatin-specific protein. The implications of these observations for mechanism of heterochromatic position effects and heterochromatin function are discussed.

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