Motohashi H, Ohta J, Engel J D, Yamamoto M
Center for Tsukuba Advanced Research Alliance and Institute of Basic Medical Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan.
Genes Cells. 1998 Oct;3(10):671-84. doi: 10.1046/j.1365-2443.1998.00222.x.
MafK serves as a required subunit of erythroid transcription factor NF-E2 and also functions with various heterodimeric CNC family proteins. MafK expression begins in early mesoderm and is observed in mesenchymal and haematopoietic cells, as well as in neurones during mouse development. In mesodermal descendants, MafK mRNA begins with a distal first exon (called IM), whereas the mRNA in neurones begins with a proximal first exon (IN).
To elucidate the mechanisms that underlie the tissue-specific transcription of the mafK gene, and to gain insights into the functions of MafK during neural development, we analysed the activity of the mafK IN promoter. A detailed investigation of mafK expression in the embryonic spinal cord revealed that IN-initiated mRNA is expressed in the ventral side of the spinal cord. Transient transfection analysis of reporter plasmids bearing the IN promoter and upstream regions revealed that the 'core' region of this promoter (nt -67 to -9) is active and that its integrity is crucial for this activity. The core region was also capable of directing the tissue-specific transcription of a reporter gene in neural cells of the spinal cord in transgenic mice in vivo.
These results demonstrate that the specific expression of mafK in neural cells is determined, at least in part, by the core region of the IN promoter.
MafK是红细胞转录因子NF-E2的必需亚基，还与多种异二聚体CNC家族蛋白共同发挥作用。在小鼠发育过程中，MafK的表达始于早期中胚层，在间充质和造血细胞以及神经元中都可观察到。在中胚层后代中，MafK mRNA起始于一个远端的第一外显子（称为IM），而神经元中的mRNA起始于一个近端的第一外显子（IN）。
为了阐明mafK基因组织特异性转录的机制，并深入了解MafK在神经发育过程中的功能，我们分析了mafK IN启动子的活性。对胚胎脊髓中mafK表达的详细研究表明，由IN起始的mRNA在脊髓腹侧表达。对携带IN启动子及上游区域的报告质粒进行瞬时转染分析表明，该启动子的“核心”区域（核苷酸-67至-9）具有活性，且其完整性对该活性至关重要。在体内转基因小鼠的脊髓神经细胞中，核心区域也能够指导报告基因的组织特异性转录。
这些结果表明，mafK在神经细胞中的特异性表达至少部分由IN启动子的核心区域决定。
