Giacca M, Pegoraro G, Gutierrez MI, Marcello A, Lusic M, Signorelli A; International Conference on AIDS.

Int Conf AIDS. 2000 Jul 9-14; 13: abstract no. WePpA1371.

M. Giacca, Padriciano, 99, 34012 Trieste, Italy, Tel.: +39 040 375 7324, Fax: +39 040 226 555, E-mail: giacca@icgeb.trieste.it

Background: In cells chronically infected with HIV-1, the integrated viral promoter is transcriptionally silent being negatively regulated by chromatin conformation. The HIV-1 Tat protein binds to the TAR sequence at the 5' end of viral mRNA and relieves this inhibition by inducing remodeling of the nucleosome arrangement downstream of the transcription initiation site. Looseness=-100000 Results: We (Marzio, G, et al. 1998. Proc. Natl. Acad. Sci. USA 95, 13519-13524) and others have already shown that Tat performs this activity by interacting with the p300 and CBP transcriptional adaptors, having histone acetyltransferase (HAT) activity. This interaction requires integrity of the basic domain of Tat and occurs through the CBP2 domain of p300 (aa. 1621-1877), a region also interacting with other cellular proteins. Tat associates with HAT activity in human nuclear extracts and binds p300/CBP both in vitro and in vivo. Furthermore, Tat induces the association of p300/CBP with the chromosomally integrated LTR promoter and functionally interacs with p300/CBP to increase transcription. Tat recruits p300/CBP through the formation of multiple protein-protein interactions that involve Tat, p300/CBP and other cellular factor(s). One of these factors is the human cellular protein AMF-1/gps2, which is also involved in the activity of two other viral transactivators, namely E2 from papillomaviruses and Tax from HTLV-I. AMF-1/gps2 interacts with Tat in vitro and is involved in the recruitment of p300/CBP to the viral LTR. Thus AMF-1/gps2 appears to be part of the chromatin remodeling/transcription complex recruited by Tat to the integrated viral promoter. Conclusions: These findings have important implications for the understanding of the molecular mechanisms of HIV-1 post-integration latency and Tat-mediated reactivation.

Publication Types:

• Meeting Abstracts

Keywords:

• Acetyltransferases
• Chromatin
• Gene Products, tat
• Genes, Regulator
• Genes, tat
• HIV-1
• Humans
• In Vitro
• Nucleosomes
• Promoter Regions (Genetics)
• Trans-Activators
• Transcription Factors
• Transcription, Genetic
• genetics

Other ID:

• GWAIDS0002647

UI: 102240141

From Meeting Abstracts