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NK 同源域转录因子 Tinman 是果蝇背血管中 seven-up 的直接激活因子。

The NK homeodomain transcription factor Tinman is a direct activator of seven-up in the Drosophila dorsal vessel.

作者信息

Ryan Kathryn M, Hendren Jill D, Helander Lynda A, Cripps Richard M

机构信息

Department of Biology, University of New Mexico, Albuquerque, NM 87131, USA.

出版信息

Dev Biol. 2007 Feb 15;302(2):694-702. doi: 10.1016/j.ydbio.2006.10.025. Epub 2006 Oct 21.

Abstract

A complex regulatory cascade is required for normal cardiac development, and many aspects of this network are conserved from Drosophila to mammals. In Drosophila, the seven-up (svp) gene, an ortholog of the vertebrate chick ovalbumin upstream promoter transcription factors (COUP-TFI and II), is initially activated in the cardiac mesoderm and is subsequently restricted to cells forming the cardiac inflow tracts. Here, we investigate svp regulation in the developing cardiac tube. Using bioinformatics, we identify a 1007-bp enhancer of svp which recapitulates its entire expression in the embryonic heart and other mesodermal derivatives, and we show that this enhancer is initially activated by the NK homeodomain factor Tinman (Tin) via two conserved Tin binding sites. Mutation of the Tin binding sites significantly reduces enhancer activity both during normal development and in response to ectopic Tin. This is the first identification of an enhancer for the complex svp gene, demonstrating the effectiveness of bioinformatics tools in assisting in unraveling transcriptional regulatory networks. Our studies define a critical component of the svp regulatory cascade and place gene regulatory events in direct apposition to the formation of critical cardiac structures.

摘要

正常的心脏发育需要一个复杂的调控级联反应,并且该网络的许多方面从果蝇到哺乳动物都是保守的。在果蝇中,七上(svp)基因是脊椎动物鸡卵清蛋白上游启动子转录因子(COUP-TFI和II)的直系同源基因,最初在心脏中胚层被激活,随后局限于形成心脏流入道的细胞。在这里,我们研究发育中的心脏管中的svp调控。利用生物信息学,我们鉴定出一个1007 bp的svp增强子,它概括了其在胚胎心脏和其他中胚层衍生物中的全部表达,并且我们表明该增强子最初由NK同源域因子锡人(Tin)通过两个保守的Tin结合位点激活。Tin结合位点的突变在正常发育过程中和对异位Tin的反应中均显著降低增强子活性。这是首次鉴定出复杂的svp基因的增强子,证明了生物信息学工具在协助揭示转录调控网络方面的有效性。我们的研究定义了svp调控级联反应的一个关键组成部分,并将基因调控事件与关键心脏结构的形成直接联系起来。

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