Recruitment of TFIIH to the HIV LTR is a rate-limiting step in the emergence of HIV from latency

Kim, Young Kyeung, Bourgeois, Cyril F, Pearson, Richard, Tyagi, Mudit, West, Michelle J, Wong, Julian, Wu, Shwu-Yuan, Chiang, Cheng-Ming and Karn, Jonathan (2006) Recruitment of TFIIH to the HIV LTR is a rate-limiting step in the emergence of HIV from latency. EMBO Journal, 25 (15). pp. 3596-3604. ISSN 0261-4189

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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.

Item Type: Article
Schools and Departments: School of Life Sciences > Biochemistry
Depositing User: Michelle West
Date Deposited: 06 Feb 2012 21:01
Last Modified: 04 May 2012 08:48
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