Regulation of human papillomavirus transcription by the differentiation-dependent epithelial factor Epoc-1/skn-1a
| Autor: | K Yukawa, Teruhito Yasui, Hitoshi Kikutani, F Hoppe-Seyler, K Butz |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Gene Expression Regulation
Viral Transcription Genetic Cellular differentiation Molecular Sequence Data Immunology Biology Microbiology Cell Line Transactivation Virology Tumor Cells Cultured Transcriptional regulation Humans Promoter Regions Genetic Papillomaviridae Transcription factor Octamer transcription factor Epithelial cell differentiation Regulation of gene expression Base Sequence Cell Differentiation Epithelial Cells Promoter Oncogene Proteins Viral Molecular biology DNA-Binding Proteins Repressor Proteins Insect Science DNA Viral Mutation Octamer Transcription Factors HeLa Cells Transcription Factors Research Article |
| Zdroj: | Journal of Virology. 70:10-16 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.70.1.10-16.1996 |
| Popis: | Human papillomavirus (HPV) early gene expression is closely linked to the differentiation status of infected epithelial cells. Typically, HPV type 16 (HPV16) or HPV18 E6 and E7 transcripts are only barely detectable within the undifferentiated basal cell layer, but their levels increase concomitantly with higher degrees of epithelial cell differentiation in suprabasal cells. A similar differentiation-dependent distribution of expression has been reported for the recently cloned epithelial cell specific transcription factor Epoc-1/skn-1a. We therefore examined whether Epoc-1/skn-1a may be directly involved in the activation of HPV E6/E7 transcription. Transient transfection studies showed that Epoc-1/skn-1a specifically stimulated the HPV16 and HPV18 E6/E7 promoters. Moreover, ectopically expressed Epoc-1/skn-1a was sufficient to stimulate HPV transcription also in nonepithelial cells. By deletion analyses, the Epoc-1/skn-1a-responsive element was mapped to the promoter-proximal portion of the HPV18 transcriptional control region. Footprint analyses and gel retardation assays demonstrated direct binding of Epoc-1/skn-1a to a hitherto uncharacterized site within this region. Mutation of the Epoc-1/skn-1a recognition site within the context of the complete HPV18 upstream regulatory region inhibited Epoc-1/skn-1a-mediated transactivation. These results show that Epoc-1/skn-1a can directly activate the E6/E7 promoter by binding to the viral transcriptional control region. Thus, Epoc-1/skn-1a may be involved in the differentiation-dependent regulation of HPV transcription. |
| Databáze: | OpenAIRE |
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