Prevalence of deletions of YY1-binding sites in episomal HPV 16 DNA from cervical cancers

Int J Cancer. 1994 Sep 15;58(6):803-8. doi: 10.1002/ijc.2910580609.


Expression of the oncogenes E6 and E7 of human papillomavirus 16 (HPV 16) appears enhanced in pre-malignant and malignant genital tumors. We recently identified a transcriptional silencer upstream of the oncogene promoter P97, comprising 4 binding sites for the cellular YY1 protein. The analysis of the long transcriptional control regions (LCR) of episomal HPV 16 DNAs from primary tumors and lymph-node metastases of 6 patients with cervical cancer revealed deletions and point mutations of YY1 binding sites in 4 cases. To test for the activity of the P97 promoter, the mutated LCRs were cloned in a luciferase reporter gene vector. A point mutation in YY1-recognition site 4, which prevents DNA-protein interaction, did not affect promoter activity, probably due to compensation by the overlapping YY1-binding site 3. However, 5.5- to 6.5-fold increased luciferase expression was obtained under the control of 3 shortened LCRs lacking 2 to 4 YY1-binding sites. A point mutation in YY1-recognition site 2, which was previously shown to stimulate P97 3.5-fold, could be detected in the HPV 16 LCRs from both primary tumor and metastasis, indicating that the mutation is a stable characteristic of HPV 16 DNA associated with the individual cancer. These findings suggest that deletions or mutations of YY1-binding sites play a significant role in over-expression of viral oncogenes and tumor progression.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Binding Sites
  • Blotting, Southern
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / virology*
  • DNA, Viral / genetics*
  • DNA, Viral / metabolism*
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism*
  • Erythroid-Specific DNA-Binding Factors
  • Female
  • Gene Deletion
  • Humans
  • Molecular Sequence Data
  • Neoplasm Metastasis
  • Oncogene Proteins, Viral / genetics
  • Oncogene Proteins, Viral / metabolism
  • Papillomaviridae / chemistry
  • Papillomaviridae / genetics*
  • Papillomaviridae / metabolism*
  • Point Mutation
  • Promoter Regions, Genetic / genetics
  • Promoter Regions, Genetic / physiology
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism*
  • Transcription Factors / physiology
  • Tumor Cells, Cultured
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / virology*
  • YY1 Transcription Factor


  • DNA, Viral
  • DNA-Binding Proteins
  • E2 protein, Human papillomavirus type 16
  • Erythroid-Specific DNA-Binding Factors
  • Oncogene Proteins, Viral
  • Transcription Factors
  • YY1 Transcription Factor
  • YY1 protein, human