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| Content Provider | PubMed Central |
|---|---|
| Author | Ferris, Andrea L. Wu, Xiaolin Hughes, Christina M. Stewart, Claudia Smith, Steven J. Milne, Thomas A. Wang, Gang G. Shun, Ming-chieh Allis, C. David Engelman, Alan Hughes, Stephen H. |
| Abstract | Lens epithelium-derived growth factor (LEDGF) fusion proteins can direct HIV-1 DNA integration to novel sites in the host genome. The C terminus of LEDGF contains an integrase binding domain (IBD), and the N terminus binds chromatin. LEDGF normally directs integrations to the bodies of expressed genes. Replacing the N terminus of LEDGF with chromatin binding domains (CBDs) from other proteins changes the specificity of HIV-1 DNA integration. We chose two well-characterized CBDs: the plant homeodomain (PHD) finger from ING2 and the chromodomain from heterochromatin binding protein 1α (HP1α). The ING2 PHD finger binds H3K4me3, a histone mark that is associated with the transcriptional start sites of expressed genes. The HP1α chromodomain binds H3K9me2,3, histone marks that are widely distributed throughout the genome. A fusion protein in which the ING2 PHD finger was linked to the LEDGF IBD directed integrations near the start sites of expressed genes. A similar fusion protein in which the HP1α chromodomain was linked to the LEDGF IBD directed integrations to sites that differed from both the PHD finger fusion–directed and LEDGF-directed integration sites. The ability to redirect HIV-1 DNA integration may help solve the problems associated with the activation of oncogenes when retroviruses are used in gene therapy. |
| Related Links | http://dx.doi.org/10.1073/pnas.0914142107 |
| Ending Page | 3140 |
| Page Count | 6 |
| Starting Page | 3135 |
| File Format | |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 7 |
| Volume Number | 107 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2010-02-16 |
| Access Restriction | Open |
| Rights Holder | National Academy of Sciences |
| Subject Keyword | General Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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