OpenAccessBelV2, France, Analysis, bibRecord, 000175

Transcription factor binding sites in the pol gene intragenic regulatory region of HIV-1 are important for virus infectivity

Identifieur interne : 000175 ( France/Analysis ); précédent : 000174; suivant : 000176

Transcription factor binding sites in the pol gene intragenic regulatory region of HIV-1 are important for virus infectivity

Auteurs : Ve Ronique Goffin ; Dominique Demonte ; Caroline Vanhulle ; Ste Phane De Walque ; Yvan De Launoit [Belgique, France] ; Arse Ne Burny ; Yves Collette [France] ; Carine Van Lint

Source :

Nucleic Acids Research [ 0305-1048 ] ; 2005.

RBID : ISTEX:849EBC0581F9AB402D25C182884AE765C3781713

Abstract

We have previously identified in the pol gene of human immunodeficiency virus type 1 (HIV-1) a new positive transcriptional regulatory element (nt 4481–4982) containing recognition sites for nuclear proteins (sites B, C, D and a GC-box) [C. Van Lint, J. Ghysdael, P. Paras, Jr, A. Burny and E. Verdin (1994) J. Virol. 68, 2632–2648]. In this study, we have further physically characterized each binding site and have shown that the transcription factors Oct-1, Oct-2, PU.1, Sp1 and Sp3 interact in vitro with the pol region. Chromatin immunoprecipitation assays using HIV-infected cell lines demonstrated in the context of chromatin that Sp1, Sp3, Oct-1 and PU.1 are recruited to the HS7 region in vivo. For each site, we have identified mutations abolishing factor binding to their cognate DNA sequences without altering the underlying amino acid sequence of the integrase. By transient transfection assays, we have demonstrated the involvement of the pol binding sites in the transcriptional enhancing activity of the intragenic region. Our functional results with multimerized wild-type and mutated pol binding sites separately (i.e. in the absence of the other sites) have demonstrated that the PU.1, Sp1, Sp3 and Oct-1 transcription factors regulate the transcriptional activity of a heterologous promoter through their respective HS7 binding sites. Finally, we have investigated the physiological role of the HS7 binding sites in HIV-1 replication and have shown that these sites are important for viral infectivity.

Url:

https://api.istex.fr/document/849EBC0581F9AB402D25C182884AE765C3781713/fulltext/pdf

DOI: 10.1093/nar/gki720

Affiliations:

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ISTEX:849EBC0581F9AB402D25C182884AE765C3781713

Le document en format XML

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<front><div type="abstract" xml:lang="en">We have previously identified in the pol gene of human immunodeficiency virus type 1 (HIV-1) a new positive transcriptional regulatory element (nt 4481–4982) containing recognition sites for nuclear proteins (sites B, C, D and a GC-box) [C. Van Lint, J. Ghysdael, P. Paras, Jr, A. Burny and E. Verdin (1994) J. Virol. 68, 2632–2648]. In this study, we have further physically characterized each binding site and have shown that the transcription factors Oct-1, Oct-2, PU.1, Sp1 and Sp3 interact in vitro with the pol region. Chromatin immunoprecipitation assays using HIV-infected cell lines demonstrated in the context of chromatin that Sp1, Sp3, Oct-1 and PU.1 are recruited to the HS7 region in vivo. For each site, we have identified mutations abolishing factor binding to their cognate DNA sequences without altering the underlying amino acid sequence of the integrase. By transient transfection assays, we have demonstrated the involvement of the pol binding sites in the transcriptional enhancing activity of the intragenic region. Our functional results with multimerized wild-type and mutated pol binding sites separately (i.e. in the absence of the other sites) have demonstrated that the PU.1, Sp1, Sp3 and Oct-1 transcription factors regulate the transcriptional activity of a heterologous promoter through their respective HS7 binding sites. Finally, we have investigated the physiological role of the HS7 binding sites in HIV-1 replication and have shown that these sites are important for viral infectivity.</div>
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Transcription factor binding sites in the pol gene intragenic regulatory region of HIV-1 are important for virus infectivity

Transcription factor binding sites in the pol gene intragenic regulatory region of HIV-1 are important for virus infectivity

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Abstract

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