Interaction and functional collaboration of p300/CBP and bHLH proteins in muscle and B-cell differentiation
Interaction and functional collaboration of p300/CBP and bHLH proteins in muscle and B-cell differentiation
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DOI：
10.1101/gad.10.19.2478
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发表时间：
1996-10-01
影响因子：
10.5
通讯作者：
Livingston, DM
中科院分区：
文献类型：
--
作者：
Eckner, R;Yao, TP;Livingston, DM
骨骼肌细胞和B淋巴细胞的分化受碱性螺旋-环-螺旋（bHLH）蛋白的调控。这两种分化程序都受到腺病毒E1A癌蛋白的抑制。对E1A突变体的分析表明，它的两种细胞结合蛋白p300和CBP控制着分化的某些方面。我们发现p300可以与组织特异性bHLH蛋白合作激活靶基因，并且只需要这些蛋白的bHLH结构域就可以刺激E盒定向转录。重要的是，bHLH蛋白激活转录的能力与E-box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-box基序。在成肌细胞中微量注射p300/CBP抗体可阻断肌源性bHLH蛋白的末端分化、细胞融合和转录活性。这些结果表明，p300/CBP的功能对细胞分化的关键方面的执行至关重要。
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.