The mechanism underlying trans-inactivation associated with dominant position effect variegation (PEV) of the Drosophila melanogaster brown gene has been addressed by a comparison with its D. virilis homologue. This comparison revealed: 86% identity between conceptual translation products of the brown gene from these two species, functional homology, as the D. virilis gene rescues a D. melanogaster null brown mutation, and conservation of the sequences required for trans-inactivation, as the D. virilis gene in D. melanogaster is subject to dominant PEV. An extended region of sequence similarity upstream of the open reading frame is observed. As the D. virilis homologue is functionally interchangeable with the D. melanogaster gene, these genes must share regulatory sequences as well as protein coding homology. These results support a model in which trans-inactivation is mediated by a heterochromatin-sensitive transcription factor.
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