Data are presented that indicate that the z locus of Drosophila melanogaster represses w locus activity, but the repression is effective only on paired or physically adjacent w loci. Various mutant alleles of z and w were combined in a series of different doses to determine the effect of dosage and physical position in the nucleus on gene expression. In z/z individuals, paired white alleles fail to be expressed, while unpaired alleles are expressed normally. The results are discussed in terms of a model postulating that the z gene product represses the transcription of w(+) by complexing with an RNA produced by part of the white locus itself. In order to be effective in repression, there must be two w(+) genes producing the RNA in a limited volume in the nucleus. Such a model necessarily imposes a specific architecture on the chromatin of interphase nuclei.
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