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| Subject Categories: Chromatin & Transcription | Microbiology & Pathogens |
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| The EMBO Journal
(2006) 25, 3596–3604, doi:10.1038/sj.emboj.7601248 Published online 27 July 2006 |
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| Recruitment of TFIIH to the HIV LTR is a rate-limiting step in the emergence of HIV from latency |
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| Young Kyeung Kim1, Cyril F Bourgeois1, 3, Richard Pearson1, Mudit Tyagi1, Michelle J West1, 4, Julian Wong1, Shwu-Yuan Wu2, Cheng-Ming Chiang2 and Jonathan Karn1 |
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1 Department of Molecular Biology and Microbiology, School of Medicine, Case Western Reserve University, Cleveland, OH, USA 2 Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH, USA To whom correspondence should be addressed Jonathan Karn, Department of Molecular Biology and Microbiology, Case School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA. Tel.: +1 216 368 3915; Fax: +1 216 368 3055; E-mails jonathan.karn@case.edu or jxk153@case.edu 3 Present address: Institut de Génétique et de Biologie Moléculaire et Cellulaire, BP 10142, 67404 Illkirch Cedex, France 4 Present address: Department of Biochemistry, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QG, UK Received 11 January 2006; Accepted 28 June 2006; Published online 27 July 2006. |
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| Abstract |
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Latently infected cells rapidly initiate HIV transcription after exposure to signals that induce NF- B. To investigate the role of TFIIH during HIV reactivation in vivo, we developed a population of Jurkat cells containing integrated, but transcriptionally silent, HIV proviruses. Surprisingly, the HIV promoter in unactivated Jurkat T cells is partially occupied and carries Mediator containing the CDK8 repressive module, TFIID and RNAP II that is hypophosphorylated and confined to the promoter region. Significantly, the promoter is devoid of TFIIH. Upon stimulation of the cells by TNF- , NF-B and TFIIH are rapidly recruited to the promoter together with additional Mediator and RNAP II, but CDK8 is lost. Detailed time courses show that the levels of TFIIH at the promoter fluctuate in parallel with NF-B recruitment to the promoter. Similarly, recombinant p65 activates HIV transcription in vitro and stimulates phosphorylation of the RNAP II CTD by the CDK7 kinase module of TFIIH. We conclude that the recruitment and activation of TFIIH represents a rate-limiting step for the emergence of HIV from latency. |
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| Keywords: CDK7, HIV latency, NF-B, Tat, TFIIH |
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