A role for LEDGF/p75 in targeting HIV DNA integration

Angela Ciuffi; Manuel Llano; Eric Poeschla; Christian Hoffmann; Jeremy Leipzig; Paul Shinn; Joseph R. Ecker; Frederic Bushman

doi:10.1038/nm1329

A role for LEDGF/p75 in targeting HIV DNA integration

Angela Ciuffi, Manuel Llano, Eric Poeschla, Christian Hoffmann, Jeremy Leipzig, Paul Shinn, Joseph R. Ecker, Frederic Bushman

Molecular Medicine

Research output: Contribution to journal › Article › peer-review

449 Scopus citations

Abstract

HIV DNA integration is favored in active genes, but the underlying mechanism is unclear. Cellular lens epithelium-derived growth factor (LEDGF/p75) binds both chromosomal DNA and HIV integrase, and might therefore direct integration by a tethering interaction. We analyzed HIV integration in cells depleted for LEDGF/p75, and found that integration was (i) less frequent in transcription units, (ii) less frequent in genes regulated by LEDGF/p75 and (iii) more frequent in GC-rich DNA. LEDGF is thus the first example of a cellular protein controlling the location of HIV integration in human cells.

Original language	English (US)
Pages (from-to)	1287-1289
Number of pages	3
Journal	Nature Medicine
Volume	11
Issue number	12
DOIs	https://doi.org/10.1038/nm1329
State	Published - Dec 2005

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1038/nm1329

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@article{6c1e1c9793d3464491ecd2fe5ea47f68,

title = "A role for LEDGF/p75 in targeting HIV DNA integration",

abstract = "HIV DNA integration is favored in active genes, but the underlying mechanism is unclear. Cellular lens epithelium-derived growth factor (LEDGF/p75) binds both chromosomal DNA and HIV integrase, and might therefore direct integration by a tethering interaction. We analyzed HIV integration in cells depleted for LEDGF/p75, and found that integration was (i) less frequent in transcription units, (ii) less frequent in genes regulated by LEDGF/p75 and (iii) more frequent in GC-rich DNA. LEDGF is thus the first example of a cellular protein controlling the location of HIV integration in human cells.",

author = "Angela Ciuffi and Manuel Llano and Eric Poeschla and Christian Hoffmann and Jeremy Leipzig and Paul Shinn and Ecker, {Joseph R.} and Frederic Bushman",

note = "Funding Information: We thank P. Bates, C. Berry, R. Doms, S. Hannenhalli and members of the Bushman, Ecker and Poeschla laboratories for discussions and M. Vanegas for help with the LEDGF/p75 knockdown cell lines. This work was supported by US National Institutes of Health grants AI52845 and AI34786, the J.B. Pendleton Charitable Trust, and R. and F. Withington (to F.B.) and the F.B. Burns Foundation (to J.R.E.) and AI47536 (to E.P.). A.C. was supported in part by a fellowship from the Swiss National Science Foundation.",

year = "2005",

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doi = "10.1038/nm1329",

language = "English (US)",

volume = "11",

pages = "1287--1289",

journal = "Nature Medicine",

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T1 - A role for LEDGF/p75 in targeting HIV DNA integration

AU - Ciuffi, Angela

AU - Llano, Manuel

AU - Poeschla, Eric

AU - Hoffmann, Christian

AU - Leipzig, Jeremy

AU - Shinn, Paul

AU - Ecker, Joseph R.

AU - Bushman, Frederic

N1 - Funding Information: We thank P. Bates, C. Berry, R. Doms, S. Hannenhalli and members of the Bushman, Ecker and Poeschla laboratories for discussions and M. Vanegas for help with the LEDGF/p75 knockdown cell lines. This work was supported by US National Institutes of Health grants AI52845 and AI34786, the J.B. Pendleton Charitable Trust, and R. and F. Withington (to F.B.) and the F.B. Burns Foundation (to J.R.E.) and AI47536 (to E.P.). A.C. was supported in part by a fellowship from the Swiss National Science Foundation.

PY - 2005/12

Y1 - 2005/12

N2 - HIV DNA integration is favored in active genes, but the underlying mechanism is unclear. Cellular lens epithelium-derived growth factor (LEDGF/p75) binds both chromosomal DNA and HIV integrase, and might therefore direct integration by a tethering interaction. We analyzed HIV integration in cells depleted for LEDGF/p75, and found that integration was (i) less frequent in transcription units, (ii) less frequent in genes regulated by LEDGF/p75 and (iii) more frequent in GC-rich DNA. LEDGF is thus the first example of a cellular protein controlling the location of HIV integration in human cells.

AB - HIV DNA integration is favored in active genes, but the underlying mechanism is unclear. Cellular lens epithelium-derived growth factor (LEDGF/p75) binds both chromosomal DNA and HIV integrase, and might therefore direct integration by a tethering interaction. We analyzed HIV integration in cells depleted for LEDGF/p75, and found that integration was (i) less frequent in transcription units, (ii) less frequent in genes regulated by LEDGF/p75 and (iii) more frequent in GC-rich DNA. LEDGF is thus the first example of a cellular protein controlling the location of HIV integration in human cells.

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A role for LEDGF/p75 in targeting HIV DNA integration

Abstract

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