TBP/TFIID-dependent activation of MyoD target genes in skeletal muscle cells

Change in the identity of the components of the transcription pre-initiation complex is proposed to control cell type-specific gene expression. Replacement of the canonical TFIID-TBP complex with TRF3/TBP2 was reported to be required for activation of muscle-gene expression. The lack of a developmental phenotype in TBP2 null mice prompted further analysis to determine whether TBP2 deficiency can compromise adult myogenesis. We show here that TBP2 null mice have an intact regeneration potential upon injury and that TBP2 is not expressed in established C2C12 muscle cell or in primary mouse MuSCs. While TFIID subunits and TBP are downregulated during myoblast differentiation, reduced amounts of these proteins form a complex that is detectable on promoters of muscle genes and is essential for their expression. This evidence demonstrates that TBP2 does not replace TBP during muscle differentiation, as previously proposed, with limiting amounts of TFIID-TBP being required to promote muscle-sp...

有研究提出，转录前起始复合物（transcription pre-initiation complex）各组分的身份转换可调控细胞类型特异性基因表达。已有研究报道，将经典TFIID-TBP复合物替换为TRF3/TBP2，是激活肌肉基因表达所必需的过程。鉴于TBP2敲除小鼠（TBP2 null mice）未出现发育表型，我们开展了进一步分析以探究TBP2缺失是否会损害成体肌发生（adult myogenesis）。本研究显示，TBP2敲除小鼠在受到损伤后仍具备完整的再生潜能；同时，在已建立的C2C12肌细胞及原代小鼠肌肉干细胞（MuSCs）中均未检测到TBP2的表达。在成肌细胞分化过程中，TFIID亚基与TBP的表达量会下调，但仍有少量此类蛋白质形成复合物，可被检测结合于肌肉基因的启动子区域，且该复合物对于肌肉基因的表达至关重要。上述证据表明，在肌分化过程中TBP2并未如此前所提出的那样取代TBP，而限量存在的TFIID-TBP复合物是促进肌肉[原文内容未完整给出]