A role for LEDGF/p75 in targeting HIV DNA integration.
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.
Ciuffi
Angela
A
University of Pennsylvania School of Medicine, Department of Microbiology, 3610 Hamilton Walk, Philadelphia, Pennsylvania 19104-6076, USA.
Llano
Manuel
M
Poeschla
Eric
E
Hoffmann
Christian
C
Leipzig
Jeremy
J
Shinn
Paul
P
Ecker
Joseph R
JR
Bushman
Frederic
F
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002460:Cell Line; D004247:DNA / Q000378:metabolism*; D020868:Gene Silencing; D006678:HIV / Q000235:genetics* / Q000502:physiology; D019427:HIV Integrase / Q000378:metabolism; D006801:Humans; D046228:Microarray Analysis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016662:Virus Integration / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; C504649:PSIP1 protein, human; D014157:Transcription Factors; D004247:DNA; D019427:HIV Integrase