Sprott Centre for Stem Cell Research, Ottawa Hospital Research Institute, and Department of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Dev Cell. 2012 Jun 12;22(6):1208-20. doi: 10.1016/j.devcel.2012.03.014. Epub 2012 May 17.
Pax3 and Pax7 regulate stem cell function in skeletal myogenesis. However, molecular insight into their distinct roles has remained elusive. Using gene expression data combined with genome-wide binding-site analysis, we show that both Pax3 and Pax7 bind identical DNA motifs and jointly activate a large panel of genes involved in muscle stem cell function. Surprisingly, in adult myoblasts Pax3 binds a subset (6.4%) of Pax7 targets. Despite a significant overlap in their transcriptional network, Pax7 regulates distinct panels of genes involved in the promotion of proliferation and inhibition of myogenic differentiation. We show that Pax7 has a higher binding affinity to the homeodomain-binding motif relative to Pax3, suggesting that intrinsic differences in DNA binding contribute to the observed functional difference between Pax3 and Pax7 binding in myogenesis. Together, our data demonstrate distinct attributes of Pax7 function and provide mechanistic insight into the nonredundancy of Pax3 and Pax7 in muscle development.
Pax3 和 Pax7 调节成肌细胞中的干细胞功能。然而，它们各自作用的分子机制仍难以捉摸。本研究结合基因表达数据和全基因组结合位点分析，结果表明 Pax3 和 Pax7 结合相同的 DNA 基序，并共同激活了一大组与肌肉干细胞功能相关的基因。令人惊讶的是，在成肌细胞中 Pax3 仅结合 Pax7 靶基因的一小部分（6.4%）。尽管它们的转录网络有显著的重叠，但 Pax7 调节参与促进增殖和抑制成肌分化的不同基因。研究表明，与 Pax3 相比，Pax7 对同源域结合基序具有更高的结合亲和力，这表明 DNA 结合的内在差异导致了 Pax3 和 Pax7 在成肌过程中的结合在功能上存在差异。综上，这些数据表明了 Pax7 功能的独特属性，并为 Pax3 和 Pax7 在肌肉发育中的非冗余性提供了机制上的见解。
