San Raffaele Scientific Institute and University Vita Salute San Raffaele, 20132 Milan, Italy.
Mol Biol Cell. 2009 Aug;20(15):3543-51. doi: 10.1091/mbc.e09-02-0114. Epub 2009 May 28.
We have analyzed the role of actin polymerization in retinoic acid (RA)-induced HoxB transcription, which is mediated by the HoxB regulator Prep1. RA induction of the HoxB genes can be prevented by the inhibition of actin polymerization. Importantly, inhibition of actin polymerization specifically affects the transcription of inducible Hox genes, but not that of their transcriptional regulators, the RARs, nor of constitutively expressed, nor of actively transcribed Hox genes. RA treatment induces the recruitment to the HoxB2 gene enhancer of a complex composed of "elongating" RNAPII, Prep1, beta-actin, and N-WASP as well as the accessory splicing components p54Nrb and PSF. We show that inhibition of actin polymerization prevents such recruitment. We conclude that inducible Hox genes are selectively sensitive to the inhibition of actin polymerization and that actin polymerization is required for the assembly of a transcription complex on the regulatory region of the Hox genes.
我们分析了肌动蛋白聚合在视黄酸(RA)诱导的 HoxB 转录中的作用,该转录由 HoxB 调节因子 Prep1 介导。肌动蛋白聚合的抑制可以阻止 RA 诱导的 HoxB 基因的转录。重要的是,肌动蛋白聚合的抑制特异性地影响诱导型 Hox 基因的转录,而不影响其转录调节剂 RAR 基因的转录,也不影响组成型表达和活跃转录的 Hox 基因的转录。RA 处理诱导“延伸”的 RNAPII、Prep1、β-肌动蛋白和 N-WASP 以及辅助剪接成分 p54Nrb 和 PSF 组成的复合物募集到 HoxB2 基因增强子。我们表明,肌动蛋白聚合的抑制阻止了这种募集。我们得出结论,诱导型 Hox 基因对肌动蛋白聚合的抑制具有选择性敏感性,并且肌动蛋白聚合对于在 Hox 基因的调节区组装转录复合物是必需的。