Identification of NFI-binding sites and cloning of NFI-cDNAs suggest a regulatory role for NFI transcription factors in olfactory neuron gene expression

Olfactory receptor neurons are responsible for the detection and signal tra nsduction of odor ligands. Several genes associated with this activity are preferentially or exclusively expressed in these neurons. Among these genes are those coding for olfactory receptors, adenylyl cyclase type III, the c yclic nucleotide gated olfactory channel I (OcNC-1), G alpha(Olf) and the o lfactory marker protein (OMP). Promoter analyses of these genes identified a binding site for the new transcription factor family O/E whose initial me mber, Olf-1, is abundantly expressed in olfactory neurons. We report here t hat the proximal promoters of three of these genes, that are selectively ex pressed in olfactory neurons, each contains a functional NFI binding site a nd that the sites have different affinities for NFI proteins indicating a r egulatory role for NFI proteins in olfactory gene expression. We further de monstrate, by cloning, that all four NFI genes are expressed in the olfacto ry nasal mucosa. Analysis by in situ hybridization illustrates that at leas t three of these gene products are expressed in the neuroepithelium in whic h the olfactory neurons reside. NFI proteins are capable of functioning as positive or negative regulators of transcription depending on the tissue, c ell-type, age, and gene in question. These multivalent functions of NFI cou ld be achieved by temporally and spatially regulated expression of distinct subsets of NFI isoforms. It now remains to characterize the tissue and cel l. specific patterns of expression of distinct NFI transcription factors du ring ontogeny and their roles in regulating gene expression. (C) 1999 Elsev ier Science B.V. Ail rights reserved.