Division of Life Science, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clearwater Bay, Kowloon, Hong Kong, China.
Cell Stem Cell. 2012 Aug 3;11(2):231-41. doi: 10.1016/j.stem.2012.05.022.
In mouse skeletal muscles, Pax7 uniquely marks muscle satellite cells and plays some important yet unknown functions at the perinatal stage. To elucidate its in vivo functions, we initiated a yeast two-hybrid screening to look for Pax7-interacting proteins and identified a previously uncharacterized Pax7- and Pax3-binding protein (Pax3/7BP). Pax3/7BP is a ubiquitously expressed nuclear protein, enriched in Pax7+ muscle precursor cells (MPCs), and serves as an indispensable adaptor for Pax7 to recruit the histone 3 lysine 4 (H3K4) methyltransferase (HMT) complex by bridging Pax7 and Wdr5. Knockdown of Pax3/7BP abolished the Pax3/7-associated H3K4 HMT activity and inhibited the proliferation of Pax7+ MPCs from young mice both in culture and in vivo. Id3 and Cdc20 were direct target genes of Pax7 and Pax3/7BP involved in the proliferation of Pax7+ MPCs. Collectively, our work establishes Pax3/7BP as an essential adaptor linking Pax3/7 with the H3K4 HMT to regulate the proliferation of MPCs.
在小鼠骨骼肌中，Pax7 独特地标记肌肉卫星细胞，并在围产期发挥一些重要但未知的功能。为了阐明其体内功能，我们启动了酵母双杂交筛选，寻找与 Pax7 相互作用的蛋白质，并鉴定了一种以前未被描述的 Pax7 和 Pax3 结合蛋白（Pax3/7BP）。Pax3/7BP 是一种普遍表达的核蛋白，在 Pax7+肌肉前体细胞（MPCs）中富集，并作为 Pax7 招募组蛋白 3 赖氨酸 4（H3K4）甲基转移酶（HMT）复合物的不可或缺的接头，通过桥接 Pax7 和 Wdr5。Pax3/7BP 的敲低消除了 Pax3/7 相关的 H3K4 HMT 活性，并抑制了年轻小鼠体内和体外培养的 Pax7+MPCs 的增殖。Id3 和 Cdc20 是 Pax7 和 Pax3/7BP 参与 Pax7+MPCs 增殖的直接靶基因。总之，我们的工作确立了 Pax3/7BP 作为一种必不可少的接头，将 Pax3/7 与 H3K4 HMT 连接起来，以调节 MPCs 的增殖。
