HIV integration site selection: analysis by massively parallel pyrosequencing reveals association with epigenetic modifications

Détails

ID Serval
serval:BIB_07CB18A97F54
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
HIV integration site selection: analysis by massively parallel pyrosequencing reveals association with epigenetic modifications
Périodique
Genome Research
Auteur(s)
Wang  G. P., Ciuffi  A., Leipzig  J., Berry  C. C., Bushman  F. D.
ISSN
1088-9051
Statut éditorial
Publié
Date de publication
08/2007
Peer-reviewed
Oui
Volume
17
Numéro
8
Pages
1186-94
Notes
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't --- Old month value: Aug
Résumé
Integration of retroviral DNA into host cell DNA is a defining feature of retroviral replication. HIV integration is known to be favored in active transcription units, which promotes efficient transcription of the viral genes, but the molecular mechanisms responsible for targeting are not fully clarified. Here we used pyrosequencing to map 40,569 unique sites of HIV integration. Computational prediction of nucleosome positions in target DNA indicated that integration sites are periodically distributed on the nucleosome surface, consistent with favored integration into outward-facing DNA major grooves in chromatin. Analysis of integration site positions in the densely annotated ENCODE regions revealed a wealth of new associations between integration frequency and genomic features. Integration was particularly favored near transcription-associated histone modifications, including H3 acetylation, H4 acetylation, and H3 K4 methylation, but was disfavored in regions rich in transcription-inhibiting modifications, which include H3 K27 trimethylation and DNA CpG methylation. Statistical modeling indicated that effects of histone modification on HIV integration were partially independent of other genomic features influencing integration. The pyrosequencing and bioinformatic methods described here should be useful for investigating many aspects of retroviral DNA integration.
Mots-clé
Chromosome Mapping/*methods DNA, Viral/metabolism Diphosphates/metabolism *Epigenesis, Genetic Gene Expression Profiling Genome HIV/*genetics Humans Jurkat Cells Models, Genetic Molecular Sequence Data Nucleosomes/metabolism Sequence Analysis, DNA Virus Integration/*genetics
Pubmed
Web of science
Open Access
Oui
Création de la notice
22/02/2008 15:45
Dernière modification de la notice
08/05/2019 14:03
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