Berkes Charlotte A, Bergstrom Donald A, Penn Bennett H, Seaver Karen J, Knoepfler Paul S, Tapscott Stephen J
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Mol Cell. 2004 May 21;14(4):465-77. doi: 10.1016/s1097-2765(04)00260-6.
Skeletal muscle differentiation is initiated by the transcription factor MyoD, which binds directly to the regulatory regions of genes expressed during skeletal muscle differentiation and initiates chromatin remodeling at specific promoters. It is not known, however, how MyoD initially recognizes its binding site in a chromatin context. Here we show that the H/C and helix III domains, two domains of MyoD that are necessary for the initiation of chromatin remodeling at the myogenin locus, together regulate a restricted subset of genes, including myogenin. These domains are necessary for the stable binding of MyoD to the myogenin promoter through an interaction with an adjacent protein complex containing the homeodomain protein Pbx, which appears to be constitutively bound at this site. This demonstrates a specific mechanism of targeting MyoD to loci in inactive chromatin and reveals a critical role of homeodomain proteins in marking specific genes for activation in the muscle lineage.
骨骼肌分化由转录因子MyoD启动，MyoD直接结合至骨骼肌分化过程中表达的基因的调控区域，并在特定启动子处启动染色质重塑。然而，尚不清楚MyoD最初如何在染色质环境中识别其结合位点。在此我们表明，H/C结构域和螺旋III结构域是MyoD在肌细胞生成素基因座启动染色质重塑所必需的两个结构域，它们共同调控包括肌细胞生成素在内的一个受限基因子集。这些结构域对于MyoD通过与包含同源结构域蛋白Pbx的相邻蛋白复合物相互作用而稳定结合至肌细胞生成素启动子是必需的，该蛋白复合物似乎组成性地结合于该位点。这证明了将MyoD靶向非活性染色质中基因座的一种特定机制，并揭示了同源结构域蛋白在标记肌肉谱系中特定基因以供激活方面的关键作用。
