Kudrycki K, Stein-Izsak C, Behn C, Grillo M, Akeson R, Margolis F L
Department of Neurosciences, Roche Institute of Molecular Biology, Roche Research Center, Nutley, New Jersey 07110.
Mol Cell Biol. 1993 May;13(5):3002-14. doi: 10.1128/mcb.13.5.3002-3014.1993.
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.
我们报告了嗅觉标记蛋白(OMP)基因5'侧翼区域内几个结构域的特征,这些结构域可能参与调控该基因以及其他嗅觉神经元特异性基因的转录。通过电泳迁移率变动分析和DNase I足迹法分析,确定了两个含有新序列基序的区域。仅用源自嗅觉神经上皮的核蛋白提取物检测到该基序与核蛋白之间的相互作用,并且这种活性在富含未成熟神经元的嗅觉上皮中更为丰富。我们将参与这种结合的一个或多个因子命名为Olf-1。Olf-1结合基序共有序列被定义为TCCCC(A/T)NGGAG。对转基因小鼠的研究表明,含有一个Olf-1基序的OMP基因0.3 kb片段足以使报告基因在嗅觉组织中特异性表达。其他一些已鉴定的序列基序也与嗅觉核蛋白提取物发生特异性相互作用。我们提出,Olf-1是一种新型的、嗅觉神经元特异性反式作用因子,参与OMP的细胞特异性表达。