HIV-1 gene expression is the major determinant regulating the rate of virus replication and, consequently, AIDS progression. Following primary infection, most infected cells produce virus. However, a small population becomes latently infected and constitutes the viral reservoir. This stable viral reservoir seriously challenges the hope of complete viral eradication. Viewed in this context, it is critical to define the molecular mechanisms involved in the establishment of transcriptional latency and the reactivation of viral expression. We show that Suv39H1, HP1gamma and histone H3Lys9 trimethylation play a major role in chromatin-mediated repression of integrated HIV-1 gene expression. Suv39H1, HP1gamma and histone H3Lys9 trimethylation are reversibly associated with HIV-1 in a transcription-dependent manner. Finally, we show in different cellular models, including PBMCs from HIV-1-infected donors, that HIV-1 reactivation could be achieved after HP1gamma RNA interference.
Suv39H1 and HP1gamma are responsible for chromatin-mediated HIV-1 transcriptional silencing and post-integration latency
du Chene, I.; Basyuk, E.; Lin, Y. L.; Triboulet, R.; Knezevich, A.; Chable-Bessia, C.; Mettling, C.; Baillat, V.; Reynes, J.; Corbeau, P.; Bertrand, E.; Marcello, A.; Emiliani, S.; Kiernan, R.; Benkirane, M.
2007-01-24 / vol 26 / pages 424-35
7601517 [pii] 10.1038/sj.emboj.7601517
Humans; Cells, Cultured; Transcriptional Activation; Histones/metabolism; Models, Biological; *Gene Silencing; Transcription, Genetic; Hela Cells; HIV-1/*physiology; Jurkat Cells; p300-CBP Transcription Factors; *Virus Integration; *Virus Latency; Cell Cycle Proteins/physiology; Chromatin/*physiology; Chromosomal Proteins, Non-Histone/*physiology; Histone Acetyltransferases/physiology; Histone-Lysine N-Methyltransferase/metabolism; HIV Long Terminal Repeat; Methyltransferases/*physiology; Positive Transcriptional Elongation Factor B/physiology; Protein Methyltransferases; Repressor Proteins/*physiology; Sp1 Transcription Factor/physiology; Transcription Factors/physiology