Papatsenko Dmitri, Levine Michael S
Department of Molecular and Cell Biology, Division of Genetics, Genomics, and Development, and Center for Integrative Genomics, University of California, Berkeley, CA 94720, USA.
Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):2901-6. doi: 10.1073/pnas.0711941105. Epub 2008 Feb 19.
The regulation of segmentation gene expression is investigated by computational modeling using quantitative expression data. Previous tissue culture assays and transgene analyses raised the possibility that Hunchback (Hb) might function as both an activator and repressor of transcription. At low concentrations, Hb activates gene expression, whereas at high concentrations it mediates repression. Under the same experimental conditions, transcription factors encoded by other gap genes appear to function as dedicated repressors. Models based on dual regulation suggest that the Hb gradient can be sufficient for establishing the initial Kruppel (Kr) expression pattern in central regions of the precellular embryo. The subsequent refinement of the Kr pattern depends on the combination of Hb and the Giant (Gt) repressor. The dual-regulation models developed for Kr also explain some of the properties of the even-skipped (eve) stripe 3+7 enhancer. Computational simulations suggest that repression results from the dimerization of Hb monomers on the DNA template.
通过使用定量表达数据的计算模型来研究分段基因表达的调控。先前的组织培养试验和转基因分析提出了驼背蛋白(Hb)可能同时作为转录激活因子和抑制因子发挥作用的可能性。在低浓度时,Hb激活基因表达,而在高浓度时它介导抑制作用。在相同的实验条件下,由其他间隙基因编码的转录因子似乎作为专门的抑制因子发挥作用。基于双重调控的模型表明,Hb梯度足以在细胞前胚胎的中央区域建立初始的克鲁佩尔(Kr)表达模式。Kr模式的后续细化取决于Hb和巨蛋白(Gt)抑制因子的组合。为Kr开发的双重调控模型也解释了偶数跳动(eve)条纹3 + 7增强子的一些特性。计算模拟表明,抑制作用是由DNA模板上Hb单体的二聚化导致的。