title: Identification of novel cellular transcription factors that regulate early promoters of human papillomavirus types 18 and 16.
abstract: BACKGROUND
  The long control region (LCR) of human papillomavirus (HPV) regulates early gene transcription by interaction with several viral and cellular transcription factors (TFs).
  
  
  METHODS
  To identify novel TFs that could influence early expression of HPV type 18 (HPV-18) and HPV type 16 (HPV-16), a high-throughput transfection array was used.
  
  
  RESULTS
  Among the 704 TFs tested, 28 activated and 36 inhibited the LCR of HPV-18 by more than 2-fold. For validation, C33 cells were cotransfected with increasing amounts of selected TF expression plasmids in addition to LCR-luciferase vectors of different molecular variants of HPV-18 and HPV-16. Among the TFs identified, only GATA3, FOXA1, and MYC have putative binding sites within the LCR sequence, as indicated using the TRANSFAC database. Furthermore, we demonstrated FOXA1 and MYC in vivo binding to the LCR of both HPV types using chromatin immunoprecipitation assay.
  
  
  CONCLUSIONS
  We identified new TFs implicated in the regulation of the LCR of HPV-18 and HPV-16. Many of these factors are mutated in cancer or are putative cancer biomarkers and could potentially be involved in the regulation of HPV early gene expression.
authors: Department of Virology, Ludwig Institute for Cancer Research, São Paulo, SP, Brazil. lsichero@gmail.com
authors: Laura
authors: L
authors: Sichero
authors: João Simão
authors: JS
authors: Sobrinho
authors: Luisa Lina
authors: LL
authors: Villa
mesh_terms: D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D014644:Genetic Variation; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000235:genetics / Q000378:metabolism; D052162:Human papillomavirus 16 / Q000235:genetics / Q000302:isolation & purification*; D052161:Human papillomavirus 18 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D015151:Immunoblotting; D011401:Promoter Regions, Genetic / Q000502:physiology*; D040081:Protein Array Analysis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000502:physiology*; D002583:Uterine Cervical Neoplasms / Q000821:virology*
chemical_list: C496499:FOXA1 protein, human; D050990:GATA3 Transcription Factor; D051541:Hepatocyte Nuclear Factor 3-alpha; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors