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Recruitment of TFIIH to the HIV LTR is a rate-limiting step in the emergence of HIV from latency
journal contribution
posted on 2023-06-08, 08:32 authored by Young Kyeung Kim, Cyril F Bourgeois, Richard Pearson, Mudit Tyagi, Michelle WestMichelle West, Julian Wong, Shwu-Yuan Wu, Cheng-Ming Chiang, Jonathan KarnLatently 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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Publication status
- Published
Journal
EMBO JournalISSN
0261-4189Publisher
Nature Publishing GroupExternal DOI
Issue
15Volume
25Page range
3596-3604Pages
9.0Department affiliated with
- Biochemistry Publications
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- No
Peer reviewed?
- Yes
Legacy Posted Date
2012-02-06Usage metrics
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