The proposed research will attempt to understand the organization and regulation of genes that behave in a peculiar manner when moved next to heterochromatin, the cytologically compacted regions of chromosomes. Two genes, the Drosophila melanogaster brown and karmoisin loci, are affected in both cis and trans by such rearrangements. Almost all other genes that are similarly juxtaposed are affected only in cis. Of the various models that have been invoked to explain these anomalies, one which proposed closely linked trans-acting regulators is supported by the results of our initial molecular investigation of the brown locus, in which we find that brown lies just between the copies of a duplicated gene. Another model which proposed that dominant variegation is caused by the production of anti-sense RNA is also consistent with the unusual organization of the region around brown. Yet another possibility is that heterochromatin can directly inactivate transcription on the homologous chromosome. In any case, it appears that the unusual behavior of the brown locus in response to position effects results from a novel form of gene organization or regulation. A thorough molecular characterization of both brown and karmoisin and the regions around them will be done. The results of this work should bear on general questions of regulatory interactions in complex eukaryotes and of position effects which can lead to abnormal expression of genes.
