Eckner R, Yao T P, Oldread E, Livingston D M
Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA.
Genes Dev. 1996 Oct 1;10(19):2478-90. doi: 10.1101/gad.10.19.2478.
Differentiation of skeletal muscle cells and B lymphocytes is regulated by basic helix-loop-helix (bHLH) proteins. Both differentiation programs are inhibited by the adenovirus E1A oncoprotein. Analysis of E1A mutants has implicated two of its cellular-binding proteins, p300 and CBP, in controlling certain aspects of differentiation. We find that p300 can cooperate with tissue-specific bHLH proteins in activating target genes and requires only the bHLH domain of such proteins to stimulate E box-directed transcription. Importantly, the ability of bHLH proteins to activate transcription correlates with the presence of p300/CBP in E box-dependent DNA-binding complexes, because both phenomena require at least two adjacent E-box motifs. Microinjection of p300/CBP antibodies into myoblasts blocks terminal differentiation, cell fusion, and transcriptional activity of myogenic bHLH proteins. These results suggest that the function of p300/CBP is essential for the execution of key aspects of cellular differentiation.
骨骼肌细胞和B淋巴细胞的分化受碱性螺旋-环-螺旋（bHLH）蛋白调控。这两种分化程序均受腺病毒E1A癌蛋白抑制。对E1A突变体的分析表明，其两种细胞结合蛋白p300和CBP参与调控分化的某些方面。我们发现，p300可与组织特异性bHLH蛋白协同激活靶基因，且仅需此类蛋白的bHLH结构域即可刺激E盒定向转录。重要的是，bHLH蛋白激活转录的能力与E盒依赖性DNA结合复合物中p300/CBP的存在相关，因为这两种现象都需要至少两个相邻的E盒基序。将p300/CBP抗体显微注射到成肌细胞中会阻断终末分化、细胞融合以及成肌bHLH蛋白的转录活性。这些结果表明，p300/CBP的功能对于细胞分化关键方面的执行至关重要。
