Waltzer Lucas, Bataillé Laetitia, Peyrefitte Sandrine, Haenlin Marc
Centre de Biologie du Développement-CNRS, 31062 Toulouse, France.
EMBO J. 2002 Oct 15;21(20):5477-86. doi: 10.1093/emboj/cdf545.
serpent (srp) encodes a GATA transcription factor essential for haematopoiesis in Drosophila. Previously, Srp was shown to contain a single GATA zinc finger of C-terminal type. Here we show that srp encodes different isoforms, generated by alternative splicing, that contain either only a C-finger (SrpC) or both a C- and an N-finger (SrpNC). The presence of the N-finger stabilizes the interaction of Srp with palindromic GATA sites and allows interaction with the Friend of GATA factor U-shaped (Ush). We have examined the respective functions of SrpC and SrpNC during embryonic haematopoiesis. Both isoforms individually rescue blood cell formation that is lacking in an srp null mutation. Interestingly, while SrpC and SrpNC activate some genes in a similar manner, they regulate others differently. Interaction between SrpNC and Ush is responsible for some but not all aspects of the distinct activities of SrpC and SrpNC. Our results suggest that the inclusion or exclusion of the N-finger in the naturally occurring isoforms of Srp can provide an effective means of extending the versatility of srp function during development.
蛇形蛋白(Srp)编码一种对果蝇造血至关重要的GATA转录因子。此前研究表明,Srp含有一个C端类型的单一GATA锌指结构。在此我们发现,srp通过可变剪接编码不同的异构体,这些异构体要么只包含一个C端锌指(SrpC),要么同时包含一个C端锌指和一个N端锌指(SrpNC)。N端锌指的存在稳定了Srp与回文GATA位点的相互作用,并使其能够与GATA因子的伙伴U形蛋白(Ush)相互作用。我们研究了SrpC和SrpNC在胚胎造血过程中的各自功能。这两种异构体各自都能挽救srp基因敲除突变体中所缺乏的血细胞形成。有趣的是,虽然SrpC和SrpNC以相似的方式激活一些基因,但它们对其他基因的调控方式不同。SrpNC与Ush之间的相互作用导致了SrpC和SrpNC不同活性的部分而非全部差异。我们的结果表明,Srp天然异构体中N端锌指的包含或缺失能够为在发育过程中扩展srp功能的多样性提供一种有效的方式。