Functional domain analysis of human HP1 isoforms in Drosophila

subtypes of HP1, a conserved non- histone chromosomal protein enriched in heterochromatin, have been identified in humans, HP1 alpha, beta and gamma. In the present study, we utilized a Drosophila system to characterize human HP1 functions. Over- expression of HP1 beta in eye imaginal discs caused abnormally patterned eyes, with reduced numbers of ommatidia, and over- expression of HP1 gamma in wing imaginal discs caused abnormal wings, in which L4 veins were gapped. These phenotypes were specific to the HP1 subtypes and appear to reflect suppressed gene expression. To determine the molecular domains of HP1 required for each specific phenotype, we constructed a series of chimeric molecules with HP1 beta and HP1 gamma. Our data show that the C- terminal chromo shadow domain ( CSD) of HP1 gamma is necessary for HP1 gamma- type phenotype, whereas for the HP1 beta- type phenotype both the chromo domain and the CSD are required. These results suggest human HP1 subtypes use different domains to suppress gene expression in Drosophila cells.