Lysine methylation of HIV-1 Tat regulates transcriptional activity of the viral LTR
<p>Abstract</p> <p>Background</p> <p>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-translatio...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2008-05-01
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| Series: | Retrovirology |
| Online Access: | http://www.retrovirology.com/content/5/1/40 |
| _version_ | 1818808568505171968 |
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| author | Flynn Elizabeth K Kehn-Hall Kylene Klase Zachary Pedati Caitlin Berro Reem Wu Weilin Easley Rebecca Van Duyne Rachel Symer David E Kashanchi Fatah |
| author_facet | Flynn Elizabeth K Kehn-Hall Kylene Klase Zachary Pedati Caitlin Berro Reem Wu Weilin Easley Rebecca Van Duyne Rachel Symer David E Kashanchi Fatah |
| author_sort | Flynn Elizabeth K |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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 <it>in vivo </it>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.</p> <p>Results</p> <p>We analyzed the association of Tat with histone methyltransferases of the SUV39-family of SET domain containing proteins <it>in vitro</it>. 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. <it>In vitro </it>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.</p> <p>Conclusion</p> <p>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.</p> |
| first_indexed | 2024-12-18T19:43:38Z |
| format | Article |
| id | doaj.art-5bd29d411d34408da756ced7c8a8686b |
| institution | Directory Open Access Journal |
| issn | 1742-4690 |
| language | English |
| last_indexed | 2024-12-18T19:43:38Z |
| publishDate | 2008-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Retrovirology |
| spelling | doaj.art-5bd29d411d34408da756ced7c8a8686b2022-12-21T20:55:22ZengBMCRetrovirology1742-46902008-05-01514010.1186/1742-4690-5-40Lysine methylation of HIV-1 Tat regulates transcriptional activity of the viral LTRFlynn Elizabeth KKehn-Hall KyleneKlase ZacharyPedati CaitlinBerro ReemWu WeilinEasley RebeccaVan Duyne RachelSymer David EKashanchi Fatah<p>Abstract</p> <p>Background</p> <p>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 <it>in vivo </it>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.</p> <p>Results</p> <p>We analyzed the association of Tat with histone methyltransferases of the SUV39-family of SET domain containing proteins <it>in vitro</it>. 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. <it>In vitro </it>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.</p> <p>Conclusion</p> <p>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.</p>http://www.retrovirology.com/content/5/1/40 |
| spellingShingle | Flynn Elizabeth K Kehn-Hall Kylene Klase Zachary Pedati Caitlin Berro Reem Wu Weilin Easley Rebecca Van Duyne Rachel Symer David E Kashanchi Fatah Lysine methylation of HIV-1 Tat regulates transcriptional activity of the viral LTR Retrovirology |
| title | Lysine methylation of HIV-1 Tat regulates transcriptional activity of the viral LTR |
| title_full | Lysine methylation of HIV-1 Tat regulates transcriptional activity of the viral LTR |
| title_fullStr | Lysine methylation of HIV-1 Tat regulates transcriptional activity of the viral LTR |
| title_full_unstemmed | Lysine methylation of HIV-1 Tat regulates transcriptional activity of the viral LTR |
| title_short | Lysine methylation of HIV-1 Tat regulates transcriptional activity of the viral LTR |
| title_sort | lysine methylation of hiv 1 tat regulates transcriptional activity of the viral ltr |
| url | http://www.retrovirology.com/content/5/1/40 |
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