Department of Cell Biology and Anatomy, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA.
Mol Biol Cell. 2010 Aug 1;21(15):2780-7. doi: 10.1091/mbc.E10-04-0290. Epub 2010 Jun 16.
Expression of the gene encoding fibroblast growth factor receptor 1 (FGFR1) and subsequent FGFR1-mediated cell signaling controls numerous developmental and disease-related processes. The transcriptional regulation of the FGFR1 gene is central to these developmental events and serves as a molecular model for understanding transcriptional control of growth factor receptor genes. The FGFR1 promoter is activated in proliferating myoblasts via several Sp1-like binding elements. These elements display varying levels of activation potential, suggesting that unique protein-DNA complexes coordinate FGFR1 gene expression via each of these sites. The Krüppel-like factor, BTEB1/KLF9, was expressed in both proliferating myoblasts and differentiated myotubes in vitro. The BTEB1 protein was nuclear-localized in both cell types. BTEB1 activated the FGFR1 promoter via interaction with the Sp1-like binding site located at -59 bp within the FGFR1 promoter. FGFR1 gene expression is down-regulated during myogenic differentiation, and FGFR1 promoter activity is correspondingly reduced. This reduction in FGFR1 promoter activity was attributable to BTEB1 interaction with the same Sp1-like binding site located at -59 bp in the FGFR1 promoter. Therefore, BTEB1 is capable of functioning as a transcriptional activator and repressor of the same promoter via the same DNA-binding element and demonstrates a novel, bimodal role of BTEB1 during myogenesis.
成纤维细胞生长因子受体 1（FGFR1）基因的表达及其随后的 FGFR1 介导的细胞信号转导控制着许多发育和疾病相关过程。FGFR1 基因的转录调控是这些发育事件的核心，是理解生长因子受体基因转录调控的分子模型。FGFR1 启动子通过几个 Sp1 样结合元件在增殖的成肌细胞中被激活。这些元件显示出不同的激活潜力，表明独特的蛋白质-DNA 复合物通过每个位点协调 FGFR1 基因表达。Krüppel 样因子 BTEB1/KLF9 在体外增殖的成肌细胞和分化的肌管中均有表达。BTEB1 蛋白在这两种细胞类型中均定位于核内。BTEB1 通过与 FGFR1 启动子中-59 bp 处的 Sp1 样结合位点相互作用激活 FGFR1 启动子。在成肌分化过程中，FGFR1 基因表达下调，FGFR1 启动子活性相应降低。这种 FGFR1 启动子活性的降低归因于 BTEB1 与 FGFR1 启动子中-59 bp 处相同的 Sp1 样结合位点的相互作用。因此，BTEB1 能够通过相同的 DNA 结合元件作为同一启动子的转录激活剂和抑制剂发挥作用，并在成肌过程中表现出 BTEB1 的一种新的、双模态作用。
