Cell cycle arrest in G2 induces human immunodeficiency virus type 1 transcriptional activation through histone acetylation and recruitment of CBP, NF-kappaB, and c-Jun to the long terminal repeat promoter.
In human immunodeficiency virus type 1 (HIV-1)-infected cells, a cell cycle arrest in G(2) increases viral expression and may represent a strategy for the virus to optimize its expression. In latently infected cells, balance between viral silencing and reactivation relies on the nucleosomal organization of the integrated long terminal repeat (LTR). It is shown here that nucleosome nuc-1, which is located downstream of the TATA box, is specifically modified when latently infected cells are arrested in G(2) by chemical inducers. Notably, histones H3 and H4 are hyperacetylated, and this modification is associated with an increased LTR-driven transcription. nuc-1 hyperacetylation is also associated with the recruitment of histone acetyltransferase CBP and transcription factors NF-kappaB and c-Jun. NF-kappaB and/or c-Jun binding to the LTR in G(2)-arrested cells appears to be required for CBP recruitment as well as for nuc-1 remodeling and viral reactivation.
Thierry
Sylvain
S
UMR 7079, Université Pierre et Marie Curie, 7 quai Saint-Bernard, 75005 Paris, France.
Marechal
Vincent
V
Rosenzwajg
Michelle
M
Sabbah
Michèle
M
Redeuilh
Gérard
G
Nicolas
Jean-Claude
JC
Gozlan
Joël
J
D000107:Acetylation; D002352:Carrier Proteins / Q000502:physiology*; D002460:Cell Line; D003345:Corticosterone; D016195:G2 Phase; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D006657:Histones / Q000378:metabolism*; D006801:Humans; D016328:NF-kappa B / Q000502:physiology*; D011401:Promoter Regions, Genetic; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology*; D020079:Terminal Repeat Sequences; D015533:Transcriptional Activation; D014775:Virus Activation
D002352:Carrier Proteins; D006657:Histones; D016328:NF-kappa B; D016755:Proto-Oncogene Proteins c-jun; D003345:Corticosterone