Giagtzoglou Nikolaos, Alifragis Pavlos, Koumbanakis Konstantinos A, Delidakis Christos
Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas, Heraklion, Greece.
Development. 2003 Jan;130(2):259-70. doi: 10.1242/dev.00206.
The decision of ectodermal cells to adopt the sensory organ precursor fate in Drosophila is controlled by two classes of basic-helix-loop-helix transcription factors: the proneural Ac and Sc activators promote neural fate, whereas the E(spl) repressors suppress it. We show here that E(spl) proteins m7 and mgamma are potent inhibitors of neural fate, even in the presence of excess Sc activity and even when their DNA-binding basic domain has been inactivated. Furthermore, these E(spl) proteins can efficiently repress target genes that lack cognate DNA binding sites, as long as these genes are bound by Ac/Sc activators. This activity of E(spl)m7 and mgamma correlates with their ability to interact with proneural activators, through which they are probably tethered on target enhancers. Analysis of reporter genes and sensory organ (bristle) patterns reveals that, in addition to this indirect recruitment of E(spl) onto enhancers via protein-protein interaction with bound Ac/Sc factors, direct DNA binding of target genes by E(spl) also takes place. Irrespective of whether E(spl) are recruited via direct DNA binding or interaction with proneural proteins, the co-repressor Groucho is always needed for target gene repression.
在果蝇中，外胚层细胞决定采用感觉器官前体命运是由两类碱性螺旋-环-螺旋转录因子控制的：神经源基因Ac和Sc激活因子促进神经命运，而E(spl)抑制因子则抑制神经命运。我们在此表明，即使存在过量的Sc活性，甚至当其DNA结合碱性结构域已失活时，E(spl)蛋白m7和mgamma仍是神经命运的有效抑制剂。此外，只要这些基因被Ac/Sc激活因子结合，这些E(spl)蛋白就能有效地抑制缺乏同源DNA结合位点的靶基因。E(spl)m7和mgamma的这种活性与其与神经源激活因子相互作用的能力相关，它们可能通过这种相互作用被拴系在靶增强子上。对报告基因和感觉器官（刚毛）模式的分析表明，除了通过与结合的Ac/Sc因子进行蛋白质-蛋白质相互作用将E(spl)间接招募到增强子上之外，E(spl)对靶基因的直接DNA结合也会发生。无论E(spl)是通过直接DNA结合还是与神经源蛋白相互作用被招募，靶基因的抑制总是需要共抑制因子Groucho。
