Author:
Van Duyne Rachel,Easley Rebecca,Wu Weilin,Berro Reem,Pedati Caitlin,Klase Zachary,Kehn-Hall Kylene,Flynn Elizabeth K,Symer David E,Kashanchi Fatah
Abstract
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.
Publisher
Springer Science and Business Media LLC
Subject
Infectious Diseases,Virology
Reference73 articles.
1. Coffin JM, Hughes SH, Varmus HE: Retroviruses. 1997, Plainview, NY, Cold Spring Harbor Laboratory Press
2. Greene WC, Peterlin BM: Charting HIV's remarkable voyage through the cell: Basic science as a passport to future therapy. Nat Med. 2002, 8: 673-680. 10.1038/nm0702-673.
3. Bohan CA, Kashanchi F, Ensoli B, Buonaguro L, Boris-Lawrie KA, Brady JN: Analysis of Tat transactivation of human immunodeficiency virus transcription in vitro. Gene Expr. 1992, 2: 391-407.
4. Feinberg MB, Baltimore D, Frankel AD: The role of Tat in the human immunodeficiency virus life cycle indicates a primary effect on transcriptional elongation. Proc Natl Acad Sci U S A. 1991, 88: 4045-4049. 10.1073/pnas.88.9.4045.
5. Kato H, Sumimoto H, Pognonec P, Chen CH, Rosen CA, Roeder RG: HIV-1 Tat acts as a processivity factor in vitro in conjunction with cellular elongation factors. Genes Dev. 1992, 6: 655-666. 10.1101/gad.6.4.655.
Cited by
73 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献