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Binding site specificity and factor redundancy in activator protein-1-driven human papillomavirus chromatin-dependent transcription.

Activator protein-1 (AP-1) regulates diverse gene responses triggered by environmental cues and virus-induced cellular stress. Although many signaling events leading to AP-1 activation have been described, the fundamental features underlying binding site selection and factor recruitment of dimeric AP-1 complexes to their target genes remain mostly uncharacterized. Using recombinant full-length human AP-1 dimers formed between c-Jun and Fos family members (c-Fos, FosB, Fra-1, Fra-2) for DNA binding and transcriptional analysis, we found that each of these AP-1 complex exhibits differential activity for distinct non-consensus AP-1 sites present in human papillomavirus (HPV), and each AP-1 complex is capable of activating transcription from in vitro-reconstituted HPV chromatin in a p300- and acetyl-CoA-dependent manner. Transcription from HPV chromatin requires AP-1-dependent and contact-driven recruitment of p300. Acetylation of dimeric AP-1 complexes by p300 enhances AP-1 binding to DNA. Using a human C-33A cervical cancer-derived cell line harboring the episomal HPV type 11 genome, we illustrate binding site selectivity recognized by c-Jun, JunB, JunD, and various Fos family members in a combinatorial and unique pattern, highlighting the diversity and importance of non-canonical binding site recognition by various AP-1 family proteins.

Pubmed ID: 21937452 RIS Download

Mesh terms: Base Sequence | Binding Sites | Cell Survival | Chromatin | Condylomata Acuminata | Conserved Sequence | DNA, Viral | E1A-Associated p300 Protein | HCT116 Cells | HeLa Cells | Histones | Human papillomavirus 11 | Humans | Nucleosome Assembly Protein 1 | Protein Multimerization | Protein Structure, Quaternary | Proto-Oncogene Proteins c-fos | Proto-Oncogene Proteins c-jun | RNA-Binding Proteins | Regulatory Sequences, Nucleic Acid | Substrate Specificity | Transcription Factor AP-1 | Transcription, Genetic

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Associated grants

  • Agency: NCI NIH HHS, Id: R01 CA103867
  • Agency: NCI NIH HHS, Id: R01 CA124760
  • Agency: NCI NIH HHS, Id: CA103867
  • Agency: NCI NIH HHS, Id: CA124760

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