Résumé : The Human T-Lymphotropic Virus 1 is a complex oncogenic retrovirus infecting around 10 to 20 millions people. HTLV-1 is responsible for two major diseases, an aggressive lymphoproliferative disease (adult T-cell Leukemia/Lymphoma) and a neurological degenerative syndrome (HTLV-1-associated myelopathy). HTLV-1 infection is characterized by viral latency of infected cells and the absence of viremia. These features are thought to be due to transcriptional silencing of proviral expression in vivo, allowing tumor development. The aim of the present work is to further elucidate the mechanisms involved in HTLV-1 transcriptional silencing and epigenetic control. We focus our work on the contribution of the cellular Sp transcription factors family and CTIP2/Bcl11b transcriptional co-factor. These factors can regulate positively and/or negatively eukaryotic transcription, depending on the promoter and/or the epigenetic environment. Our laboratory has recently demonstrated that CTIP2 is associated to at least two distinct nuclear complexes: the inactive P-TEFb complex, and a chromatin-modifying complex containing histone-deacetylases and -methyltransferase. We demonstrated that CTIP2 repressed Tax-transactivated HTLV-1 transcription. It has been reported that CTIP2 interacts with the histone acetyltransferase p300 and is involved in transcriptional activation of the IL-2 promoter in T lymphocytes. We postulate that the function of CTIP2 might be modulated by post-translational modifications. We evaluated post-translational modifications of overexpressed CTIP2 protein and identified at least 2 acetylated residues as well as other modified residues. Interestingly, we showed that the substitution of a single particular acetylable residue by an arginine, a non-acetylable residue, impeded global acetylation of CTIP2 and interfered with the ability of CTIP2 to repress Tax-mediated HTLV-1 transactivation. Functional role of the CTIP2 modified residues will be further presented.A better understanding of the epigenetic and non-epigenetic mechanisms responsible for HTLV-1 transcriptional repression could bring new insights into oncogenic mechanisms associated with CTIP2 transcriptional regulation in humans.