Deciphering the code for retroviral integration target site selection

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License: CC BY 4.0
Serval ID
serval:BIB_355C2C6C4713
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Deciphering the code for retroviral integration target site selection
Journal
PLoS Comput Biol
Author(s)
Santoni F. A., Hartley O., Luban J.
ISSN
1553-7358 (Electronic)
ISSN-L
1553-734X
Publication state
Published
Issued date
2010
Volume
6
Number
11
Pages
e1001008
Language
english
Notes
Santoni, Federico Andrea
Hartley, Oliver
Luban, Jeremy
eng
R01 AI059159/AI/NIAID NIH HHS/
R01AI59159/AI/NIAID NIH HHS/
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
PLoS Comput Biol. 2010 Nov 24;6(11):e1001008. doi: 10.1371/journal.pcbi.1001008.
Abstract
Upon cell invasion, retroviruses generate a DNA copy of their RNA genome and integrate retroviral cDNA within host chromosomal DNA. Integration occurs throughout the host cell genome, but target site selection is not random. Each subgroup of retrovirus is distinguished from the others by attraction to particular features on chromosomes. Despite extensive efforts to identify host factors that interact with retrovirion components or chromosome features predictive of integration, little is known about how integration sites are selected. We attempted to identify markers predictive of retroviral integration by exploiting Precision-Recall methods for extracting information from highly skewed datasets to derive robust and discriminating measures of association. ChIPSeq datasets for more than 60 factors were compared with 14 retroviral integration datasets. When compared with MLV, PERV or XMRV integration sites, strong association was observed with STAT1, acetylation of H3 and H4 at several positions, and methylation of H2AZ, H3K4, and K9. By combining peaks from ChIPSeq datasets, a supermarker was identified that localized within 2 kB of 75% of MLV proviruses and detected differences in integration preferences among different cell types. The supermarker predicted the likelihood of integration within specific chromosomal regions in a cell-type specific manner, yielding probabilities for integration into proto-oncogene LMO2 identical to experimentally determined values. The supermarker thus identifies chromosomal features highly favored for retroviral integration, provides clues to the mechanism by which retrovirus integration sites are selected, and offers a tool for predicting cell-type specific proto-oncogene activation by retroviruses.
Keywords
Algorithms, Animals, Cell Line, Chi-Square Distribution, Chromatin/chemistry/genetics, Chromatin Immunoprecipitation, Cluster Analysis, Computational Biology/*methods, CpG Islands/genetics, Databases, Genetic, Genetic Markers, Genome/genetics, Host-Pathogen Interactions/genetics/physiology, Humans, Mice, Retroviridae/genetics/pathogenicity/*physiology, STAT1 Transcription Factor/genetics, Sequence Analysis, DNA, Virus Integration/genetics/*physiology
Pubmed
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20/05/2019 13:52
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30/04/2021 7:09
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