Differential gene silencing by trans-heterochromatin in Drosophila melanogaster.

The brown(Dominant) (bw(D)) allele contains a large insertion of heterochromatin leading to the trans-inactivation of the wild-type allele in bw(D)/bw(+) heterozygous flies. This silencing is correlated with the localization of bw(+) to a region of the interphase nucleus containing centric heterochromatin. We have used a series of transgene constructs inserted in the vicinity of the bw locus to demarcate both the extent of bw(D) influence along the chromosome and the relative sensitivities of various genes.

Repetitive arrays containing a housekeeping gene have altered polytene chromosome morphology in Drosophila.

Much of our understanding of gene and chromatin organization has been developed from observation of polytene chromosomes. We describe an experimental approach using transgenes that has allowed us to observe local changes in polytene morphology. A composite P transposon that contains a fusion between the regulatory region of Prat, a purine synthesis gene, and brown (bw), an eye pigment reporter, was transformed into the 65A10 polytene band and subjected to P-transposase mutagenesis.

Copy number and orientation determine the susceptibility of a gene to silencing by nearby heterochromatin in Drosophila.

The classical phenomenon of position-effect variegation (PEV) is the mosaic expression that occurs when a chromosomal rearrangement moves a euchromatic gene near heterochromatin. A striking feature of this phenomenon is that genes far away from the junction with heterochromatin can be affected, as if the heterochromatic state "spreads." We have investigated classical PEV of a Drosophila brown transgene affected by a heterochromatic junction approximately 60 kb away.

Dosage dependent modifiers of white alleles in Drosophila melanogaster.

As part of a study to identify dosage-sensitive modifiers of the white eye colour locus and the retrotransposon, copia, a segmental aneuploid screen was conducted. It surveys the autosomal complement of the genome for dosage dependent modifiers of white, including ones effective upon retrotransposon insertion-induced alleles. Several regions were found which, when present as a segmental trisomy, affected one or more of the alleles tested in a strong and consistent fashion.

Epigene conversion: a proposal with implications for gene mapping in humans.

Epigenetic modification of DNA is now recognized as a potentially important factor in the inheritance and expression of some mutations; its ability to complicate human genetic analysis is concurrently becoming apparent. One unusual form of epigenetic modification, dominant position-effect variegation (PEV), has been used as a model for Huntington disease. In dominant PEV, a fully dominant mutant phenotype results from stable epigenetic inactivation of an allele adjacent to the structural alteration (cis-inactivation) combined with a complementary inactivation of the homologous normal allele (trans-inactivation).