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Microarray-Based Sketches of the HERV Transcriptome Landscape

Human endogenous retroviruses (HERVs) are spread throughout the genome and their long terminal repeats (LTRs) constitute a wide collection of putative regulatory sequences. Phylogenetic similarities and the profusion of integration sites, two inherent characteristics of transposable elements, make i...

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Autores principales: Pérot, Philippe, Mugnier, Nathalie, Montgiraud, Cécile, Gimenez, Juliette, Jaillard, Magali, Bonnaud, Bertrand, Mallet, François
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3386233/
https://www.ncbi.nlm.nih.gov/pubmed/22761958
http://dx.doi.org/10.1371/journal.pone.0040194
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author Pérot, Philippe
Mugnier, Nathalie
Montgiraud, Cécile
Gimenez, Juliette
Jaillard, Magali
Bonnaud, Bertrand
Mallet, François
author_facet Pérot, Philippe
Mugnier, Nathalie
Montgiraud, Cécile
Gimenez, Juliette
Jaillard, Magali
Bonnaud, Bertrand
Mallet, François
author_sort Pérot, Philippe
collection PubMed
description Human endogenous retroviruses (HERVs) are spread throughout the genome and their long terminal repeats (LTRs) constitute a wide collection of putative regulatory sequences. Phylogenetic similarities and the profusion of integration sites, two inherent characteristics of transposable elements, make it difficult to study individual locus expression in a large-scale approach, and historically apart from some placental and testis-regulated elements, it was generally accepted that HERVs are silent due to epigenetic control. Herein, we have introduced a generic method aiming to optimally characterize individual loci associated with 25-mer probes by minimizing cross-hybridization risks. We therefore set up a microarray dedicated to a collection of 5,573 HERVs that can reasonably be assigned to a unique genomic position. We obtained a first view of the HERV transcriptome by using a composite panel of 40 normal and 39 tumor samples. The experiment showed that almost one third of the HERV repertoire is indeed transcribed. The HERV transcriptome follows tropism rules, is sensitive to the state of differentiation and, unexpectedly, seems not to correlate with the age of the HERV families. The probeset definition within the U3 and U5 regions was used to assign a function to some LTRs (i.e. promoter or polyA) and revealed that (i) autonomous active LTRs are broadly subjected to operational determinism (ii) the cellular gene density is substantially higher in the surrounding environment of active LTRs compared to silent LTRs and (iii) the configuration of neighboring cellular genes differs between active and silent LTRs, showing an approximately 8 kb zone upstream of promoter LTRs characterized by a drastic reduction in sense cellular genes. These gathered observations are discussed in terms of virus/host adaptive strategies, and together with the methods and tools developed for this purpose, this work paves the way for further HERV transcriptome projects.
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spelling pubmed-33862332012-07-03 Microarray-Based Sketches of the HERV Transcriptome Landscape Pérot, Philippe Mugnier, Nathalie Montgiraud, Cécile Gimenez, Juliette Jaillard, Magali Bonnaud, Bertrand Mallet, François PLoS One Research Article Human endogenous retroviruses (HERVs) are spread throughout the genome and their long terminal repeats (LTRs) constitute a wide collection of putative regulatory sequences. Phylogenetic similarities and the profusion of integration sites, two inherent characteristics of transposable elements, make it difficult to study individual locus expression in a large-scale approach, and historically apart from some placental and testis-regulated elements, it was generally accepted that HERVs are silent due to epigenetic control. Herein, we have introduced a generic method aiming to optimally characterize individual loci associated with 25-mer probes by minimizing cross-hybridization risks. We therefore set up a microarray dedicated to a collection of 5,573 HERVs that can reasonably be assigned to a unique genomic position. We obtained a first view of the HERV transcriptome by using a composite panel of 40 normal and 39 tumor samples. The experiment showed that almost one third of the HERV repertoire is indeed transcribed. The HERV transcriptome follows tropism rules, is sensitive to the state of differentiation and, unexpectedly, seems not to correlate with the age of the HERV families. The probeset definition within the U3 and U5 regions was used to assign a function to some LTRs (i.e. promoter or polyA) and revealed that (i) autonomous active LTRs are broadly subjected to operational determinism (ii) the cellular gene density is substantially higher in the surrounding environment of active LTRs compared to silent LTRs and (iii) the configuration of neighboring cellular genes differs between active and silent LTRs, showing an approximately 8 kb zone upstream of promoter LTRs characterized by a drastic reduction in sense cellular genes. These gathered observations are discussed in terms of virus/host adaptive strategies, and together with the methods and tools developed for this purpose, this work paves the way for further HERV transcriptome projects. Public Library of Science 2012-06-28 /pmc/articles/PMC3386233/ /pubmed/22761958 http://dx.doi.org/10.1371/journal.pone.0040194 Text en Pérot et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Pérot, Philippe
Mugnier, Nathalie
Montgiraud, Cécile
Gimenez, Juliette
Jaillard, Magali
Bonnaud, Bertrand
Mallet, François
Microarray-Based Sketches of the HERV Transcriptome Landscape
title Microarray-Based Sketches of the HERV Transcriptome Landscape
title_full Microarray-Based Sketches of the HERV Transcriptome Landscape
title_fullStr Microarray-Based Sketches of the HERV Transcriptome Landscape
title_full_unstemmed Microarray-Based Sketches of the HERV Transcriptome Landscape
title_short Microarray-Based Sketches of the HERV Transcriptome Landscape
title_sort microarray-based sketches of the herv transcriptome landscape
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3386233/
https://www.ncbi.nlm.nih.gov/pubmed/22761958
http://dx.doi.org/10.1371/journal.pone.0040194
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