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Analysis of CpG methylation sites and CGI among human papillomavirus DNA genomes

BACKGROUND: The Human Papillomavirus (HPV) genome is divided into early and late coding sequences, including 8 open reading frames (ORFs) and a regulatory region (LCR). Viral gene expression may be regulated through epigenetic mechanisms, including cytosine methylation at CpG dinucleotides. We have...

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Autores principales: Galván, Silvia C, Martínez-Salazar, Martha, Galván, Víctor M, Méndez, Rocío, Díaz-Contreras, Gibran T, Alvarado-Hermida, Moisés, Alcántara-Silva, Rogelio, García-Carrancá, Alejandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3293833/
https://www.ncbi.nlm.nih.gov/pubmed/22118413
http://dx.doi.org/10.1186/1471-2164-12-580
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author Galván, Silvia C
Martínez-Salazar, Martha
Galván, Víctor M
Méndez, Rocío
Díaz-Contreras, Gibran T
Alvarado-Hermida, Moisés
Alcántara-Silva, Rogelio
García-Carrancá, Alejandro
author_facet Galván, Silvia C
Martínez-Salazar, Martha
Galván, Víctor M
Méndez, Rocío
Díaz-Contreras, Gibran T
Alvarado-Hermida, Moisés
Alcántara-Silva, Rogelio
García-Carrancá, Alejandro
author_sort Galván, Silvia C
collection PubMed
description BACKGROUND: The Human Papillomavirus (HPV) genome is divided into early and late coding sequences, including 8 open reading frames (ORFs) and a regulatory region (LCR). Viral gene expression may be regulated through epigenetic mechanisms, including cytosine methylation at CpG dinucleotides. We have analyzed the distribution of CpG sites and CpG islands/clusters (CGI) among 92 different HPV genomes grouped in function of their preferential tropism: cutaneous or mucosal. We calculated the proportion of CpG sites (PCS) for each ORF and calculated the expected CpG values for each viral type. RESULTS: CpGs are underrepresented in viral genomes. We found a positive correlation between CpG observed and expected values, with mucosal high-risk (HR) virus types showing the smallest O/E ratios. The ranges of the PCS were similar for most genomic regions except E4, where the majority of CpGs are found within islands/clusters. At least one CGI belongs to each E2/E4 region. We found positive correlations between PCS for each viral ORF when compared with the others, except for the LCR against four ORFs and E6 against three other ORFs. The distribution of CpG islands/clusters among HPV groups is heterogeneous and mucosal HR-HPV types exhibit both lower number and shorter island sizes compared to cutaneous and mucosal Low-risk (LR) HPVs (all of them significantly different). CONCLUSIONS: There is a difference between viral and cellular CpG underrepresentation. There are significant correlations between complete genome PCS and a lack of correlations between several genomic region pairs, especially those involving LCR and E6. L2 and L1 ORF behavior is opposite to that of oncogenes E6 and E7. The first pair possesses relatively low numbers of CpG sites clustered in CGIs while the oncogenes possess a relatively high number of CpG sites not associated to CGIs. In all HPVs, E2/E4 is the only region with at least one CGI and shows a higher content of CpG sites in every HPV type with an identified E4. The mucosal HR-HPVs show either the shortest CGI size, followed by the mucosal LR-HPVs and lastly by the cutaneous viral subgroup, and a trend to the lowest CGI number, followed by the cutaneous viral subgroup and lastly by the mucosal LR-HPVs.
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spelling pubmed-32938332012-03-06 Analysis of CpG methylation sites and CGI among human papillomavirus DNA genomes Galván, Silvia C Martínez-Salazar, Martha Galván, Víctor M Méndez, Rocío Díaz-Contreras, Gibran T Alvarado-Hermida, Moisés Alcántara-Silva, Rogelio García-Carrancá, Alejandro BMC Genomics Research Article BACKGROUND: The Human Papillomavirus (HPV) genome is divided into early and late coding sequences, including 8 open reading frames (ORFs) and a regulatory region (LCR). Viral gene expression may be regulated through epigenetic mechanisms, including cytosine methylation at CpG dinucleotides. We have analyzed the distribution of CpG sites and CpG islands/clusters (CGI) among 92 different HPV genomes grouped in function of their preferential tropism: cutaneous or mucosal. We calculated the proportion of CpG sites (PCS) for each ORF and calculated the expected CpG values for each viral type. RESULTS: CpGs are underrepresented in viral genomes. We found a positive correlation between CpG observed and expected values, with mucosal high-risk (HR) virus types showing the smallest O/E ratios. The ranges of the PCS were similar for most genomic regions except E4, where the majority of CpGs are found within islands/clusters. At least one CGI belongs to each E2/E4 region. We found positive correlations between PCS for each viral ORF when compared with the others, except for the LCR against four ORFs and E6 against three other ORFs. The distribution of CpG islands/clusters among HPV groups is heterogeneous and mucosal HR-HPV types exhibit both lower number and shorter island sizes compared to cutaneous and mucosal Low-risk (LR) HPVs (all of them significantly different). CONCLUSIONS: There is a difference between viral and cellular CpG underrepresentation. There are significant correlations between complete genome PCS and a lack of correlations between several genomic region pairs, especially those involving LCR and E6. L2 and L1 ORF behavior is opposite to that of oncogenes E6 and E7. The first pair possesses relatively low numbers of CpG sites clustered in CGIs while the oncogenes possess a relatively high number of CpG sites not associated to CGIs. In all HPVs, E2/E4 is the only region with at least one CGI and shows a higher content of CpG sites in every HPV type with an identified E4. The mucosal HR-HPVs show either the shortest CGI size, followed by the mucosal LR-HPVs and lastly by the cutaneous viral subgroup, and a trend to the lowest CGI number, followed by the cutaneous viral subgroup and lastly by the mucosal LR-HPVs. BioMed Central 2011-11-25 /pmc/articles/PMC3293833/ /pubmed/22118413 http://dx.doi.org/10.1186/1471-2164-12-580 Text en Copyright ©2011 Galván et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Galván, Silvia C
Martínez-Salazar, Martha
Galván, Víctor M
Méndez, Rocío
Díaz-Contreras, Gibran T
Alvarado-Hermida, Moisés
Alcántara-Silva, Rogelio
García-Carrancá, Alejandro
Analysis of CpG methylation sites and CGI among human papillomavirus DNA genomes
title Analysis of CpG methylation sites and CGI among human papillomavirus DNA genomes
title_full Analysis of CpG methylation sites and CGI among human papillomavirus DNA genomes
title_fullStr Analysis of CpG methylation sites and CGI among human papillomavirus DNA genomes
title_full_unstemmed Analysis of CpG methylation sites and CGI among human papillomavirus DNA genomes
title_short Analysis of CpG methylation sites and CGI among human papillomavirus DNA genomes
title_sort analysis of cpg methylation sites and cgi among human papillomavirus dna genomes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3293833/
https://www.ncbi.nlm.nih.gov/pubmed/22118413
http://dx.doi.org/10.1186/1471-2164-12-580
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