Motohashi H, Katsuoka F, Shavit J A, Engel J D, Yamamoto M
Center for Tsukuba Advanced Research Alliance and Institute of Basic Medical Sciences University of Tsukuba 1-1-1 Tennoudai 305-8577, Tsukuba, Japan.
Cell. 2000 Dec 8;103(6):865-75. doi: 10.1016/s0092-8674(00)00190-2.
The small Maf transcription factor proteins bind to Maf Recognition Elements (MAREs) by dimerizing with CNC proteins or themselves. We undertook experiments to clarify the functional relationship between the small Mafs and their partners in vivo. Embryos expressing abundant transgene-derived MafK died of severe anemia, while lines expressing lower levels of small Maf lived to adulthood. Megakaryocytes from the latter overexpressing lines exhibited reduced proplatelet formation and MARE-dependent transcription, phenocopying mafG null mutant mice. When the mafG null mutants were bred to small Maf-overexpressing transgenic animals, both loss- and gain-of-function phenotypes were reversed. These results provide direct in vivo evidence that transcriptional regulation through MARE elements hinges on an exquisitely sensitive balance of activating CNC molecules and their small Maf partners.
小Maf转录因子蛋白通过与CNC蛋白或自身二聚化，从而与Maf识别元件（MAREs）结合。我们开展了实验，以阐明小Maf蛋白与其体内伙伴之间的功能关系。表达大量转基因衍生的MafK的胚胎死于严重贫血，而表达较低水平小Maf的品系则存活至成年。来自后一组过表达品系的巨核细胞表现出原血小板形成减少和MARE依赖性转录，这与mafG基因敲除突变小鼠的表型相似。当将mafG基因敲除突变体与过表达小Maf的转基因动物杂交时，功能丧失和功能获得的表型均得到逆转。这些结果提供了直接的体内证据，表明通过MARE元件的转录调控取决于激活CNC分子及其小Maf伙伴之间极其敏感的平衡。
