Both PCE-1/RX and OTX/CRX interactions are necessary for photoreceptor-specific gene expression

Both PCE-1/RX and OTX/CRX interactions are necessary for photoreceptor-specific gene expression
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DOI:
10.1074/jbc.275.2.1152
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发表时间:
2000-01-14
影响因子:
4.8
通讯作者:
Shinohara, T
Shinohara, T
中科院分区:
生物学2区
文献类型:
--
作者:
Kimura, A;Singh, D;Shinohara, T

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RX,一种对眼睛正常发育必不可少的含有同源结构域的蛋白质(Mathers,P.H. Grinberg,A.,Mahon,K.一、Jamrich,M.(1997)Nature 387,603-607),结合光感受器细胞特异性抑制蛋白启动子中的光感受器保守元件-1(PCE-1/Ret 1)并刺激基因表达。RX存在于许多视网膜细胞类型中,包括感光细胞。结合OTX元件以刺激启动子活性的另一种含有同源结构域的蛋白CRX仅在感光细胞中发现(Chen,S.,王,英-地L.,Nie,Z.,孙,H.,列侬,G.,Copeland,N. G.,Gillbert,D. J. Jenkins,N.一、和Zack,D. J.(1997)Neuron 19,1017-1030; Furukawa,T.,Morrow,E. M.,和Cepko,C. L.(1997)Cell 91,531-541)。结合试验和细胞培养研究表明,PCE-1和OTX元件以及至少两种不同的调节因子RX和CRX对于高水平的感光细胞限制性基因表达是必需的。因此,光感受器特异性可以通过多个启动子元件与光感受器特异性调节因子和存在于密切相关的细胞谱系中的因子的组合相互作用来实现。
RX, a homeodomain-containing protein essential for proper eye development (Mathers, P. H. Grinberg, A., Mahon, K. A., and Jamrich, M. (1997) Nature 387, 603-607), binds to the photoreceptor conserved element-1 (PCE-1/Ret 1) in the photoreceptor cell-specific arrestin promoter and stimulates gene expression. RX is found in many retinal cell types including photoreceptor cells. Another homeodomain-containing protein, CRX, which binds to the OTX element to stimulate promoter activity, is found exclusively in photoreceptor cells (Chen, S., Wang, Q. L., Nie, Z., Sun, H., Lennon, G., Copeland, N. G., Gillbert, D. J. Jenkins, N. A., and Zack, D. J. (1997) Neuron 19, 1017-1030; Furukawa, T., Morrow, E. M., and Cepko, C. L. (1997) Cell 91, 531-541). Binding assay and cell culture studies indicate that both PCE-1 and OTX elements and at least two different regulatory factors RX and CRX are necessary for high level, photoreceptor cell-restricted gene expression. Thus, photoreceptor specificity can be achieved by multiple promoter elements interacting with a combination of both photoreceptor-specific regulatory factors and factors present in closely related cell lineages.