E2F1 inhibition of transcription activation by myogenic basic helix-loop-helix regulators.
Cellular transcription factor E2F1 is thought to regulate the expression of genes important for cell cycle progression and cell proliferation. Deregulated E2F1 expression induces S-phase entry in quiescent cells and inhibits myogenic differentiation. We show here that E2F1 inhibits the activation of gene transcription by myogenic basic helix-loop-helix proteins myoD and myogenin. Transfection assay using different deletion constructs indicates that both the DNA binding and the transactivation domains of E2F1 are required for its inhibition of myoD transcription activation. However, the retinoblastoma protein (RB) binding domain is not required. Furthermore, co-transfection with the RB, which inhibits the transcription activity of E2F1, can also repress E2F1 inhibition of myoD transactivation. These results suggest an essential role of E2F1-mediated transcription in its inhibition of myogenesis.
Wang
J
J
Department of Cardiology, Children's Hospital, Boston, MA 02115, USA.
Huang
Q
Q
Tang
W
W
Nadal-Ginard
B
B
D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D003402:Creatine Kinase / Q000187:drug effects / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D018257:Helix-Loop-Helix Motifs / Q000187:drug effects / Q000235:genetics; D051379:Mice; D009132:Muscles / Q000166:cytology; D017570:MyoD Protein / Q000187:drug effects / Q000235:genetics*; D018008:Myogenin / Q000187:drug effects / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D016160:Retinoblastoma Protein / Q000235:genetics / Q000494:pharmacology; D056465:Retinoblastoma-Binding Protein 1; D017384:Sequence Deletion; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology*; D014158:Transcription, Genetic
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493754:E2f1 protein, mouse; D017570:MyoD Protein; C503801:Myog protein, mouse; D018008:Myogenin; D011994:Recombinant Proteins; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors; D003402:Creatine Kinase