{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T02:57:46Z","timestamp":1792724266244,"version":"4.5.0"},"reference-count":34,"publisher":"National Academy of Sciences","issue":"7","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,2,16]]},"abstract":"<jats:p>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 1\u03b1 (HP1\u03b1). The ING2 PHD finger binds H3K4me3, a histone mark that is associated with the transcriptional start sites of expressed genes. The HP1\u03b1 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 HP1\u03b1 chromodomain was linked to the LEDGF IBD directed integrations to sites that differed from both the PHD finger fusion\u2013directed 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.<\/jats:p>","DOI":"10.1073\/pnas.0914142107","type":"journal-article","created":{"date-parts":[[2010,2,1]],"date-time":"2010-02-01T22:51:30Z","timestamp":1265064690000},"page":"3135-3140","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":131,"title":["Lens epithelium-derived growth factor fusion proteins redirect HIV-1 DNA integration"],"prefix":"10.1073","volume":"107","author":[{"given":"Andrea L.","family":"Ferris","sequence":"first","affiliation":[{"name":"HIV Drug Resistance Program, National Cancer Institute, Frederick, MD 21702;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolin","family":"Wu","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Technology, SAIC-Frederick, Inc., Frederick, MD 21702;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina M.","family":"Hughes","sequence":"additional","affiliation":[{"name":"Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, NY 10065; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Stewart","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Technology, SAIC-Frederick, Inc., Frederick, MD 21702;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven J.","family":"Smith","sequence":"additional","affiliation":[{"name":"HIV Drug Resistance Program, National Cancer Institute, Frederick, MD 21702;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Milne","sequence":"additional","affiliation":[{"name":"Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, NY 10065; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang G.","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, NY 10065; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Chieh","family":"Shun","sequence":"additional","affiliation":[{"name":"Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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