title: Binding site specificity and factor redundancy in activator protein-1-driven human papillomavirus chromatin-dependent transcription.
abstract: 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.
authors.affiliation: Simmons Comprehensive Cancer Center, Dallas, Texas 75390, USA.
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Wang
authors.forename: Shwu-Yuan
authors.initials: SY
authors.lastname: Wu
authors.forename: A-Young
authors.initials: AY
authors.lastname: Lee
authors.forename: Cheng-Ming
authors.initials: CM
authors.lastname: Chiang
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D002470:Cell Survival; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D003218:Condylomata Acuminata / Q000821:virology; D017124:Conserved Sequence; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D050881:E1A-Associated p300 Protein / Q000378:metabolism; D045325:HCT116 Cells; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D052140:Human papillomavirus 11 / Q000235:genetics*; D006801:Humans; D056490:Nucleosome Assembly Protein 1 / Q000378:metabolism; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D013379:Substrate Specificity; D018808:Transcription Factor AP-1 / Q000737:chemistry* / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: C411647:A1CF protein, human; D002843:Chromatin; D004279:DNA, Viral; D006657:Histones; D056490:Nucleosome Assembly Protein 1; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D016601:RNA-Binding Proteins; D018808:Transcription Factor AP-1; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human