Yang X, van Beest M, Clevers H, Jones T, Hursh D A, Mortin M A
Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Development. 2000 Sep;127(17):3695-702. doi: 10.1242/dev.127.17.3695.
Drosophila T cell factor (dTcf) mediates transcriptional activation in the presence of Wingless signalling and repression in its absence. Wingless signalling is required for the correct expression of decapentaplegic (dpp), a Transforming Growth Factor (beta) family member, in parasegments 3 and 7 of the Drosophila visceral mesoderm. Here we demonstrate that a dpp enhancer element, which directs expression of a reporter gene in the visceral mesoderm in a pattern indistinguishable from dpp, has two functional dTcf binding sites. Mutations that reduce or eliminate Wingless signalling abolish dpp reporter gene expression in parasegment 3 and reduce it in parasegment 7 while ectopic expression of Wingless signalling components expand reporter gene expression anteriorly in the visceral mesoderm. However, mutation of the dTcf binding sites in the dpp enhancer results in ectopic expression of reporter gene expression throughout the visceral mesoderm, with no diminution of expression in the endogenous sites of expression. These results demonstrate that the primary function of dTcf binding to the dpp enhancer is repression throughout the visceral mesoderm and that activation by Wingless signalling is probably not mediated via these dTcf binding sites to facilitate correct dpp expression in the visceral mesoderm.
果蝇T细胞因子(dTcf)在存在无翅信号时介导转录激活,在无该信号时介导转录抑制。在果蝇内脏中胚层的第3和第7副节中,转化生长因子(β)家族成员——果蝇的DPP基因(decapentaplegic,dpp)的正确表达需要无翅信号。在这里,我们证明了一个dpp增强子元件,它能在内脏中胚层中指导报告基因的表达,其模式与dpp难以区分,该元件有两个功能性dTcf结合位点。减少或消除无翅信号的突变会消除第3副节中dpp报告基因的表达,并降低第7副节中的表达,而无翅信号成分的异位表达会使报告基因在内脏中胚层中向前扩展表达。然而,dpp增强子中dTcf结合位点的突变会导致报告基因在内脏中胚层中异位表达,且在内源表达位点的表达没有减少。这些结果表明,dTcf与dpp增强子结合的主要功能是在内脏中胚层中进行抑制,无翅信号的激活可能不是通过这些dTcf结合位点介导的,以促进dpp在内脏中胚层中的正确表达。