Ooe Norihisa, Saito Koichi, Oeda Kenji, Nakatuka Iwao, Kaneko Hideo
Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., Konohana-ku, Osaka 554-8558, Japan.
Gene. 2007 Oct 1;400(1-2):122-30. doi: 10.1016/j.gene.2007.06.005. Epub 2007 Jun 14.
The basic helix-loop-helix/Per-Arnt-Sim (bHLH-PAS) homology protein family is an important class of transcriptional regulators that are involved in a wide variety of biological processes. In a previous study, we characterized a novel bHLH-PAS factor 'NXF' as a new member of the mammalian bHLH-PAS family. If model animals have ortholog genes for NXF, they might have advantages for characterization of its function and regulation in vivo. Here we document cDNA cloning and characterization of putative NXF homolog genes (for NXF-like-factors) in Drosophila and C. elegans. Some conservation of the exon-intron gene architecture was noted in the bHLH-PAS domains among NXF-like-factors and human NXF. The NXF-like-factors selectively interacted with an Arnt ortholog in vitro assay. Moreover, they selectively associated with the mammalian NXF:Arnt2 binding element in the presence of the Arnt ortholog, and synergistically activated a mammalian NXF:Arnt-responsive promoter. These data strongly suggest that the Drosophila and C. elegans NXF-like-factors reported here are homologs of mammalian NXF. Further elucidation of whether they are true orthologs with the same function in vivo is now necessary.
基本螺旋-环-螺旋/Per-Arnt-Sim（bHLH-PAS）同源蛋白家族是一类重要的转录调节因子，参与多种生物学过程。在先前的一项研究中，我们将一种新型bHLH-PAS因子“NXF”鉴定为哺乳动物bHLH-PAS家族的新成员。如果模式动物具有NXF的直系同源基因，那么它们可能在体内对其功能和调控的表征方面具有优势。在此，我们报道了果蝇和秀丽隐杆线虫中假定的NXF同源基因（NXF样因子）的cDNA克隆及表征。在NXF样因子和人类NXF的bHLH-PAS结构域中，外显子-内含子基因结构存在一些保守性。在体外实验中，NXF样因子与一种Arnt直系同源物选择性相互作用。此外，在Arnt直系同源物存在的情况下，它们与哺乳动物NXF:Arnt2结合元件选择性结合，并协同激活哺乳动物NXF:Arnt反应性启动子。这些数据有力地表明，本文报道的果蝇和秀丽隐杆线虫NXF样因子是哺乳动物NXF的同源物。现在有必要进一步阐明它们在体内是否为具有相同功能的真正直系同源物。
