Kajihara Miwako, Sone Hirohito, Amemiya Michiyo, Katoh Yasutake, Isogai Masashi, Shimano Hitoshi, Yamada Nobuhiro, Takahashi Satoru
Department of Internal Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba 305-8575, Japan.
Biochem Biophys Res Commun. 2003 Dec 19;312(3):831-42. doi: 10.1016/j.bbrc.2003.10.196.
Large Maf transcription factors, which are members of the basic leucine zipper (b-Zip) superfamily, have been reported to be involved in embryonic development and cell differentiation. Previously, we isolated a novel zebrafish large Maf cDNA, somite Maf1 (SMaf1), which possesses transactivational activity within its N-terminus domain. To elucidate SMaf1 function in mammals, we tried to isolate the mouse homologue of zebrafish SMaf1. We isolated the mouse homologue of zebrafish SMaf1, which is the same molecule as the recently reported MafA. MafA mRNA was detected in formed somites, head neural tube, and liver cells in the embryos. In the adult mouse, MafA transcript was amplified in the brain, lung, spleen, and kidney by RT-PCR. MafA mRNA was also detectable in beta-cell line. Next, we analyzed the transcriptional activity of MafA using rat insulin promoters I and II (RIPI and II), since a part of RIP sequence was similar to the Maf recognition element (MARE) and MafA was expressed in pancreatic beta cells. MafA was able to activate transcription from RIPII, but not RIPI, in a dose dependent manner and the activity was dependent on RIPE3b/C1 sequences. In addition, the amount of MafA protein was regulated by glucose concentration. These results indicate that MafA is the homologue of zebrafish SMaf1 and acts as a transcriptional activator of the insulin gene promoter through the RIPE3b element.
大Maf转录因子是碱性亮氨酸拉链（b-Zip）超家族的成员，据报道其参与胚胎发育和细胞分化。此前，我们分离出一种新的斑马鱼大Maf cDNA，即体节Maf1（SMaf1），其在N端结构域内具有反式激活活性。为阐明SMaf1在哺乳动物中的功能，我们试图分离斑马鱼SMaf1的小鼠同源物。我们分离出了斑马鱼SMaf1的小鼠同源物，它与最近报道的MafA是同一分子。在胚胎的形成体节、头部神经管和肝细胞中检测到了MafA mRNA。在成年小鼠中，通过RT-PCR在脑、肺、脾和肾中扩增出了MafA转录本。在β细胞系中也可检测到MafA mRNA。接下来，我们使用大鼠胰岛素启动子I和II（RIPI和II）分析了MafA的转录活性，因为RIP序列的一部分与Maf识别元件（MARE）相似，且MafA在胰腺β细胞中表达。MafA能够以剂量依赖的方式激活RIPII的转录，但不能激活RIPI的转录，且该活性依赖于RIPE3b/C1序列。此外，MafA蛋白的量受葡萄糖浓度调节。这些结果表明，MafA是斑马鱼SMaf1的同源物，并通过RIPE3b元件作为胰岛素基因启动子的转录激活因子。
