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Differences in Transcriptional Activity of Human Papillomavirus Type 6 Molecular Variants in Recurrent Respiratory Papillomatosis
A significant proportion of recurrent respiratory papillomatosis (RRP) is caused by human papillomavirus type 6 (HPV-6). The long control region (LCR) contains cis-elements for regulation of transcription. Our aim was to characterize LCR HPV-6 variants in RRP cases, compare promoter activity of thes...
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Published in: | PloS one 2015-07, Vol.10 (7), p.e0132325-e0132325 |
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creator | Measso do Bonfim, Caroline Simão Sobrinho, João Lacerda Nogueira, Rodrigo Salgado Kupper, Daniel Cardoso Pereira Valera, Fabiana Lacerda Nogueira, Maurício Villa, Luisa Lina Rahal, Paula Sichero, Laura |
description | A significant proportion of recurrent respiratory papillomatosis (RRP) is caused by human papillomavirus type 6 (HPV-6). The long control region (LCR) contains cis-elements for regulation of transcription. Our aim was to characterize LCR HPV-6 variants in RRP cases, compare promoter activity of these isolates and search for cellular transcription factors (TFs) that could explain the differences observed. The complete LCR from 13 RRP was analyzed. Transcriptional activity of 5 variants was compared using luciferase assays. Differences in putative TFs binding sites among variants were revealed using the TRANSFAC database. Chromatin immunoprecipation (CHIP) and luciferase assays were used to evaluate TF binding and impact upon transcription, respectively. Juvenile-onset RRP cases harbored exclusively HPV-6vc related variants, whereas among adult-onset cases HPV-6a variants were more prevalent. The HPV-6vc reference was more transcriptionally active than the HPV-6a reference. Active FOXA1, ELF1 and GATA1 binding sites overlap variable nucleotide positions among isolates and influenced LCR activity. Furthermore, our results support a crucial role for ELF1 on transcriptional downregulation. We identified TFs implicated in the regulation of HPV-6 early gene expression. Many of these factors are mutated in cancer or are putative cancer biomarkers, and must be further studied. |
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The long control region (LCR) contains cis-elements for regulation of transcription. Our aim was to characterize LCR HPV-6 variants in RRP cases, compare promoter activity of these isolates and search for cellular transcription factors (TFs) that could explain the differences observed. The complete LCR from 13 RRP was analyzed. Transcriptional activity of 5 variants was compared using luciferase assays. Differences in putative TFs binding sites among variants were revealed using the TRANSFAC database. Chromatin immunoprecipation (CHIP) and luciferase assays were used to evaluate TF binding and impact upon transcription, respectively. Juvenile-onset RRP cases harbored exclusively HPV-6vc related variants, whereas among adult-onset cases HPV-6a variants were more prevalent. The HPV-6vc reference was more transcriptionally active than the HPV-6a reference. Active FOXA1, ELF1 and GATA1 binding sites overlap variable nucleotide positions among isolates and influenced LCR activity. Furthermore, our results support a crucial role for ELF1 on transcriptional downregulation. We identified TFs implicated in the regulation of HPV-6 early gene expression. Many of these factors are mutated in cancer or are putative cancer biomarkers, and must be further studied.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0132325</identifier><identifier>PMID: 26151558</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Age ; Analysis ; Base Sequence ; Binding sites ; Biomarkers ; Cancer ; Cell Line ; Chromatin ; Cloning ; Deoxyribonucleic acid ; Discipline ; DNA ; GATA-1 protein ; Gene expression ; Gene regulation ; Genetic aspects ; Genetic transcription ; Genetic Variation ; Genomes ; Human papillomavirus ; Human papillomavirus 6 - genetics ; Humans ; Laboratories ; Luciferase ; Medicine ; Molecular biology ; Molecular Sequence Data ; Oncology ; Otolaryngology ; Papilloma ; Papillomavirus infections ; Papillomavirus Infections - genetics ; Papillomavirus Infections - virology ; Papillomaviruses ; Plasmids ; Promoter Regions, Genetic ; Protein Binding ; Respiratory Tract Infections - genetics ; Respiratory Tract Infections - virology ; Surgery ; Transcription factors ; Transcription Factors - metabolism ; Transcription, Genetic</subject><ispartof>PloS one, 2015-07, Vol.10 (7), p.e0132325-e0132325</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Measso do Bonfim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Measso do Bonfim et al 2015 Measso do Bonfim et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-58f36710dd9e7ae7539518cf7154442e78cb7aab073e8d14a70bf193ccbeba8a3</citedby><cites>FETCH-LOGICAL-c692t-58f36710dd9e7ae7539518cf7154442e78cb7aab073e8d14a70bf193ccbeba8a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1694701534/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1694701534?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26151558$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Angeletti, Peter C.</contributor><creatorcontrib>Measso do Bonfim, Caroline</creatorcontrib><creatorcontrib>Simão Sobrinho, João</creatorcontrib><creatorcontrib>Lacerda Nogueira, Rodrigo</creatorcontrib><creatorcontrib>Salgado Kupper, Daniel</creatorcontrib><creatorcontrib>Cardoso Pereira Valera, Fabiana</creatorcontrib><creatorcontrib>Lacerda Nogueira, Maurício</creatorcontrib><creatorcontrib>Villa, Luisa Lina</creatorcontrib><creatorcontrib>Rahal, Paula</creatorcontrib><creatorcontrib>Sichero, Laura</creatorcontrib><title>Differences in Transcriptional Activity of Human Papillomavirus Type 6 Molecular Variants in Recurrent Respiratory Papillomatosis</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>A significant proportion of recurrent respiratory papillomatosis (RRP) is caused by human papillomavirus type 6 (HPV-6). 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The long control region (LCR) contains cis-elements for regulation of transcription. Our aim was to characterize LCR HPV-6 variants in RRP cases, compare promoter activity of these isolates and search for cellular transcription factors (TFs) that could explain the differences observed. The complete LCR from 13 RRP was analyzed. Transcriptional activity of 5 variants was compared using luciferase assays. Differences in putative TFs binding sites among variants were revealed using the TRANSFAC database. Chromatin immunoprecipation (CHIP) and luciferase assays were used to evaluate TF binding and impact upon transcription, respectively. Juvenile-onset RRP cases harbored exclusively HPV-6vc related variants, whereas among adult-onset cases HPV-6a variants were more prevalent. The HPV-6vc reference was more transcriptionally active than the HPV-6a reference. Active FOXA1, ELF1 and GATA1 binding sites overlap variable nucleotide positions among isolates and influenced LCR activity. Furthermore, our results support a crucial role for ELF1 on transcriptional downregulation. We identified TFs implicated in the regulation of HPV-6 early gene expression. Many of these factors are mutated in cancer or are putative cancer biomarkers, and must be further studied.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26151558</pmid><doi>10.1371/journal.pone.0132325</doi><oa>free_for_read</oa></addata></record> |
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subjects | Age Analysis Base Sequence Binding sites Biomarkers Cancer Cell Line Chromatin Cloning Deoxyribonucleic acid Discipline DNA GATA-1 protein Gene expression Gene regulation Genetic aspects Genetic transcription Genetic Variation Genomes Human papillomavirus Human papillomavirus 6 - genetics Humans Laboratories Luciferase Medicine Molecular biology Molecular Sequence Data Oncology Otolaryngology Papilloma Papillomavirus infections Papillomavirus Infections - genetics Papillomavirus Infections - virology Papillomaviruses Plasmids Promoter Regions, Genetic Protein Binding Respiratory Tract Infections - genetics Respiratory Tract Infections - virology Surgery Transcription factors Transcription Factors - metabolism Transcription, Genetic |
title | Differences in Transcriptional Activity of Human Papillomavirus Type 6 Molecular Variants in Recurrent Respiratory Papillomatosis |
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