Transcriptional regulation of human papillomavirus type 18 P105 promoter by the co-activator CBP.
Human papillomaviruses (HPVs) are the etiological agents of cervical cancer, with HPV-16 and 18 being the representative types of the higher risk group. The expression of the viral genes with transforming activity (E6 and E7) is controlled by the upstream regulatory region (URR), a segment of the viral genome that contains elements recognized by several transcription factors.


OBJECTIVE
We have analyzed the participation of the cellular co-activator CBP on the transcriptional regulation of the HPV-18 URR.


METHODS
We generated mutants and 5' end deletion constructs derived from the HPV-18 URR and evaluated their transcriptional activity performing transient co-transfection assays on C-33A cells with a plasmid that over-expresses the co-activator CBP. We also performed quantitative chromatin immunoprecipitation assays to analyze the participation of the co-activator CBP on the HPV-18 P105 promoter.


RESULTS
Our results demonstrate that in C-33A cells CBP acts as a strong activator of the HPV-18 P105 promoter by a mechanism that depends on the integrity of the SP1-binding site, directly correlating with the acetylation of the histone H3 that is involved in nucleosomal stability.


CONCLUSIONS
We propose a mechanism of regulation of the HPV-18 P105 promoter by the cellular co-activator CBP, recruited by the transcription factor SP1.
Valencia-Hernández
Armando
A
Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del IPN, México, México.
Cuevas-Bennett
Christian
C
Garrido
Efraín
E
D002478:Cells, Cultured; D004279:DNA, Viral / Q000235:genetics; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D052161:Human papillomavirus 18 / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000502:physiology*; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*; D050880:p300-CBP Transcription Factors / Q000502:physiology*
D004279:DNA, Viral; D016329:Sp1 Transcription Factor; D050880:p300-CBP Transcription Factors