Wang M M, Tsai R Y, Schrader K A, Reed R R
Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, Johns Hopkins School of Medicine, Baltimore, Maryland 21205-2185.
Mol Cell Biol. 1993 Sep;13(9):5805-13. doi: 10.1128/mcb.13.9.5805-5813.1993.
Genes which mediate odorant signal transduction are expressed at high levels in neurons of the olfactory epithelium. The molecular mechanism governing the restricted expression of these genes likely involves tissue-specific DNA binding proteins which coordinately activate transcription through sequence-specific interactions with olfactory promoter regions. We have identified binding sites for the olfactory neuron-specific transcription factor, Olf-1, in the sequences surrounding the transcriptional initiation site of five olfactory neuron-specific genes. The Olf-1 binding sites described define the consensus sequence YTCCCYRGGGAR. In addition, we have identified a second binding site, the U site, in the olfactory cyclic nucleotide gated channel and type III cyclase promoters, which binds factors present in all tissue examined. These experiments support a model in which expression of Olf-1 in the sensory neurons coordinately activates a set of olfactory neuron-specific genes. Furthermore, expression of a subset of these genes may be modulated by additional binding factors.
介导气味信号转导的基因在嗅觉上皮神经元中高水平表达。控制这些基因受限表达的分子机制可能涉及组织特异性DNA结合蛋白,这些蛋白通过与嗅觉启动子区域的序列特异性相互作用来协调激活转录。我们在五个嗅觉神经元特异性基因转录起始位点周围的序列中鉴定出了嗅觉神经元特异性转录因子Olf-1的结合位点。所描述的Olf-1结合位点定义了共有序列YTCCCYRGGGAR。此外,我们在嗅觉环核苷酸门控通道和III型环化酶启动子中鉴定出了第二个结合位点,即U位点,它能结合所有检测组织中存在的因子。这些实验支持了一个模型,即感觉神经元中Olf-1的表达协调激活一组嗅觉神经元特异性基因。此外,这些基因的一个子集的表达可能会受到其他结合因子的调节。