Olf-1-binding site: characterization of an olfactory neuron-specific promoter motif.
We report characterization of several domains within the 5' flanking region of the olfactory marker protein (OMP) gene that may participate in regulating transcription of this and other olfactory neuron-specific genes. Analysis by electrophoretic mobility shift assay and DNase I footprinting identifies two regions that contain a novel sequence motif. Interactions between this motif and nuclear proteins were detected only with nuclear protein extracts derived from olfactory neuroepithelium, and this activity is more abundant in olfactory epithelium enriched in immature neurons. We have designated a factor(s) involved in this binding as Olf-1. The Olf-1-binding motif consensus sequence was defined as TCCCC(A/T)NGGAG. Studies with transgenic mice indicate that a 0.3-kb fragment of the OMP gene containing one Olf-1 motif is sufficient for olfactory tissue-specific expression of the reporter gene. Some of the other identified sequence motifs also interact specifically with olfactory nuclear protein extracts. We propose that Olf-1 is a novel, olfactory neuron-specific trans-acting factor involved in the cell-specific expression of OMP.
Kudrycki
K
K
Department of Neurosciences, Roche Institute of Molecular Biology, Roche Research Center, Nutley, New Jersey 07110.
Stein-Izsak
C
C
Behn
C
C
Grillo
M
M
Akeson
R
R
Margolis
F L
FL
D000375:Aging / Q000502:physiology; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003850:Deoxyribonuclease I; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics*; D009474:Neurons / Q000502:physiology*; D009830:Olfactory Bulb / Q000502:physiology*; D051842:Olfactory Marker Protein; D009831:Olfactory Mucosa / Q000502:physiology*; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D009928:Organ Specificity; D016133:Polymerase Chain Reaction / Q000379:methods; D011401:Promoter Regions, Genetic; D051381:Rats; D014158:Transcription, Genetic; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D051842:Olfactory Marker Protein; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; C497598:Omp protein, mouse; C497599:Omp protein, rat; D004247:DNA; D003850:Deoxyribonuclease I; D001616:beta-Galactosidase