From genotype to olfactory neuron phenotype: the role of the Olf-1-binding site.

The highly organized pattern of gene expression leading to the determination of cellular phenotype derives from the interplay between genetic and epigenetic factors. This is mediated in part by distinctive DNA sequence motifs present in the regulatory regions of various genes and the transcription factors with which they interact. The phenotype of olfactory neurons is determined in part by the selective expression of novel isoforms of several genes involved in chemosensory transduction. To characterize the mechanisms determining olfactory neuron phenotype we have been studying the olfactory marker protein (OMP), the first olfactory-specific protein to be isolated and cloned. The temporal and spatial expression of OMP is regulated stringently and is highly restricted to mature olfactory neurons in all vertebrates from amphibians to humans. Identification of the specific elements responsible for regulating the expression of the OMP gene will elucidate the mechanisms leading to the determination of olfactory neuron phenotype. Using a combined in vivo (transgenic mice) and in vitro (electrophoretic mobility shift assays and DNase I footprinting) approach, we have identified and characterized a novel genomic motif that binds an olfactory tissue nuclear protein(s) that we designate Olf-1. We propose that Olf-1 is a novel olfactory-specific transacting factor responsible for directing the expression of genes containing the Olf-1 motif in olfactory neurons. Thus it may play a role in regulating the expression of genes associated with neuronal turnover and olfactory transduction.