Suv39H1 and HP1gamma are responsible for chromatin-mediated HIV-1 transcriptional silencing and post-integration latency

Isaure du Chéné; Euguenia Basyuk; Yea-Lih Lin; Robinson Triboulet; Anna Knezevich; Christine Chable-Bessia; Clement Mettling; Vincent Baillat; Jacques Reynes; Pierre Corbeau; Edouard Bertrand; Alessandro Marcello; Stephane Emiliani; Rosemary Kiernan; Monsef Benkirane

doi:10.1038/sj.emboj.7601517

Suv39H1 and HP1gamma are responsible for chromatin-mediated HIV-1 transcriptional silencing and post-integration latency

EMBO J. 2007 Jan 24;26(2):424-35. doi: 10.1038/sj.emboj.7601517.

Authors

Isaure du Chéné¹, Euguenia Basyuk, Yea-Lih Lin, Robinson Triboulet, Anna Knezevich, Christine Chable-Bessia, Clement Mettling, Vincent Baillat, Jacques Reynes, Pierre Corbeau, Edouard Bertrand, Alessandro Marcello, Stephane Emiliani, Rosemary Kiernan, Monsef Benkirane

Affiliation

¹ Laboratoire de Virologie Moléculaire, Institut de Génétique Humaine, UPR 1142, Montpellier, France.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Cycle Proteins / physiology
Cells, Cultured
Chromatin / physiology*
Chromosomal Proteins, Non-Histone / physiology*
Gene Silencing*
HIV Long Terminal Repeat
HIV-1 / physiology*
HeLa Cells
Histone Acetyltransferases / physiology
Histone Methyltransferases
Histone-Lysine N-Methyltransferase / metabolism
Histones / metabolism
Humans
Jurkat Cells
Methyltransferases / physiology*
Models, Biological
Positive Transcriptional Elongation Factor B / physiology
Protein Methyltransferases
Repressor Proteins / physiology*
Sp1 Transcription Factor / physiology
Transcription Factors / physiology
Transcription, Genetic
Transcriptional Activation
Virus Integration*
Virus Latency*
p300-CBP Transcription Factors

Substances

CBX3 protein, human
Cell Cycle Proteins
Chromatin
Chromosomal Proteins, Non-Histone
Histones
Repressor Proteins
Sp1 Transcription Factor
Transcription Factors
SUV39H1 protein, human
Histone Methyltransferases
Methyltransferases
Protein Methyltransferases
Histone-Lysine N-Methyltransferase
Histone Acetyltransferases
p300-CBP Transcription Factors
p300-CBP-associated factor
Positive Transcriptional Elongation Factor B