Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Institute for Genomics and Systems Biology and Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA.
Dev Cell. 2014 Oct 13;31(1):100-13. doi: 10.1016/j.devcel.2014.08.005.
In Drosophila embryos, a nuclear gradient of the Dorsal (Dl) transcription factor directs differential gene expression along the dorsoventral (DV) axis, translating it into distinct domains that specify future mesodermal, neural, and ectodermal territories. However, the mechanisms used to differentially position gene expression boundaries along this axis are not fully understood. Here, using a combination of approaches, including mutant phenotype analyses and chromatin immunoprecipitation, we show that the transcription factor Suppressor of Hairless, Su(H), helps define dorsal boundaries for many genes expressed along the DV axis. Synthetic reporter constructs also provide molecular evidence that Su(H) binding sites support repression and act to counterbalance activation through Dl and the ubiquitous activator Zelda. Our study highlights a role for broadly expressed repressors, like Su(H), and organization of transcription factor binding sites within cis-regulatory modules as important elements controlling spatial domains of gene expression to facilitate flexible positioning of boundaries across the entire DV axis.
在果蝇胚胎中,Dorsal(Dl)转录因子的核梯度沿背腹(DV)轴指导差异基因表达,将其转化为指定未来中胚层、神经和外胚层区域的不同域。然而,用于沿该轴差异定位基因表达边界的机制尚未完全理解。在这里,我们使用包括突变表型分析和染色质免疫沉淀在内的多种方法表明,转录因子 Hairless 抑制因子(Su(H))有助于确定许多沿 DV 轴表达的基因的背侧边界。合成报告基因构建体也提供了分子证据表明,Su(H)结合位点支持抑制作用,并通过 Dl 和普遍的激活因子 Zelda 来平衡激活作用。我们的研究强调了广泛表达的抑制剂(如 Su(H))的作用,以及转录因子结合位点在顺式调控模块内的组织作为控制基因表达空间域的重要因素,以促进整个 DV 轴上边界的灵活定位。