Interaction and functional collaboration of p300/CBP and bHLH proteins in muscle and B-cell differentiation.
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.
Eckner
R
R
Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA.
Yao
T P
TP
Oldread
E
E
Livingston
D M
DM
D016475:3T3 Cells; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D001665:Binding Sites; D050882:CREB-Binding Protein; D002454:Cell Differentiation; D002457:Cell Extracts; D002459:Cell Fusion / Q000502:physiology; D004247:DNA / Q000378:metabolism; D004274:DNA, Recombinant; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D050881:E1A-Associated p300 Protein; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D064326:MEF2 Transcription Factors; D051379:Mice; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal; D018482:Muscle, Skeletal / Q000166:cytology* / Q000254:growth & development; D017570:MyoD Protein / Q000032:analysis / Q000378:metabolism; D018006:Myogenic Regulatory Factors; D018008:Myogenin / Q000032:analysis / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D051820:TCF Transcription Factors; D015534:Trans-Activators; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D015533:Transcriptional Activation / Q000502:physiology
D002457:Cell Extracts; D004274:DNA, Recombinant; D004268:DNA-Binding Proteins; D007143:Immunoglobulin Heavy Chains; D064326:MEF2 Transcription Factors; C503799:MYOG protein, human; D017570:MyoD Protein; C503801:Myog protein, mouse; D018006:Myogenic Regulatory Factors; D018008:Myogenin; D009687:Nuclear Proteins; D051820:TCF Transcription Factors; C544912:TCF7L1 protein, human; C544913:Tcf7l1 protein, mouse; D015534:Trans-Activators; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors; D004247:DNA; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; C494364:Crebbp protein, mouse; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse