SMYD2-Mediated Histone Methylation Contributes to HIV-1 Latency.
In: Cell host & microbe, Jg. 21 (2017-05-01), Heft 5
Online
academicJournal
- 569 - 579.e6
Transcriptional latency of HIV is a last barrier to viral eradication. Chromatin-remodeling complexes and post-translational histone modifications likely play key roles in HIV-1 reactivation, but the underlying mechanisms are incompletely understood. We performed an RNAi-based screen of human lysine methyltransferases and identified the SET and MYND domain-containing protein 2 (SMYD2) as an enzyme that regulates HIV-1 latency. Knockdown of SMYD2 or its pharmacological inhibition reactivated latent HIV-1 in T cell lines and in primary CD4+ T cells. SMYD2 associated with latent HIV-1 promoter chromatin, which was enriched in monomethylated lysine 20 at histone H4 (H4K20me1), a mark lost in cells lacking SMYD2. Further, we find that lethal 3 malignant brain tumor 1 (L3MBTL1), a reader protein with chromatin-compacting properties that recognizes H4K20me1, was recruited to the latent HIV-1 promoter in a SMYD2-dependent manner. We propose that a SMYD2-H4K20me1-L3MBTL1 axis contributes to HIV-1 latency and can be targeted with small-molecule SMYD2 inhibitors.
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SMYD2-Mediated Histone Methylation Contributes to HIV-1 Latency.
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Autor/in / Beteiligte Person: | Boehm, Daniela ; Jeng, Mark ; Camus, Gregory ; Gramatica, Andrea ; Schwarzer, Roland ; Johnson, Jeffrey R ; Hull, Philip A ; Montano, Mauricio ; Sakane, Naoki ; Pagans, Sara ; Godin, Robert ; Deeks, Steven G ; Krogan, Nevan J ; Greene, Warner C ; Ott, Melanie |
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Zeitschrift: | Cell host & microbe, Jg. 21 (2017-05-01), Heft 5 |
Veröffentlichung: | eScholarship, University of California, 2017 |
Medientyp: | academicJournal |
Umfang: | 569 - 579.e6 |
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