Journal article
Lysine methylation of HIV-1 Tat regulates transcriptional activity of the viral LTR
Retrovirology, v 5(1), 40
22 May 2008
PMID: 18498648
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Background: The rate of transcription of the HIV-1 viral genome is mediated by the interaction of the viral protein Tat with the LTR and other transcriptional machinery. These specific interactions can be affected by the state of post-translational modifications on Tat. Previously, we have shown that Tat can be phosphorylated and acetylated in vivo resulting in an increase in the rate of transcription. In the present study, we investigated whether Tat could be methylated on lysine residues, specifically on lysine 50 and 51, and whether this modification resulted in a decrease of viral transcription from the LTR.
Results: We analyzed the association of Tat with histone methyltransferases of the SUV39-family of SET domain containing proteins in vitro. Tat was found to associate with both SETDB1 and SETDB2, two enzymes which exhibit methyltransferase activity. siRNA against SETDB1 transfected into cell systems with both transient and integrated LTR reporter genes resulted in an increase in transcription of the HIV-LTR in the presence of suboptimal levels of Tat. In vitro methylation assays with Tat peptides containing point mutations at lysines 50 and 51 showed an increased incorporation of methyl groups on lysine 51, however, both residues indicated susceptibility for methylation.
Conclusion: The association of Tat with histone methyltransferases and the ability for Tat to be methylated suggests an interesting mechanism of transcriptional regulation through the recruitment of chromatin remodeling proteins to the HIV-1 promoter.
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Details
- Title
- Lysine methylation of HIV-1 Tat regulates transcriptional activity of the viral LTR
- Creators
- Rachel Van Duyne - Washington University Medical CenterRebecca Easley - George Washington UniversityWeilin Wu - Washington University Medical CenterReem Berro - Washington University Medical CenterCaitlin Pedati - Washington University Medical CenterZachary Klase - Washington University Medical CenterKylene Kehn-Hall - George Washington UniversityElizabeth K. Flynn - Frederick National Laboratory for Cancer ResearchDavid E. Symer - National Cancer InstituteFatah Kashanchi - University of Southern California
- Publication Details
- Retrovirology, v 5(1), 40
- Publisher
- Springer Nature
- Number of pages
- 13
- Grant note
- AI071903-01; R21 AI071903 / NIAID NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) R21AI071903 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) Z01BC010631 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) NIH0011255384; Z01 BC010631-04 / Intramural NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000256479100001
- Scopus ID
- 2-s2.0-44949118480
- Other Identifier
- 991021902505404721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Virology