{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:40:24Z","timestamp":1781106024247,"version":"3.54.1"},"reference-count":56,"publisher":"National Academy of Sciences","issue":"34","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,8,21]]},"abstract":"<jats:p>\n                    The epigenetic silencing of exogenous transcriptional units integrated into the genome represents a critical problem both for long-term gene therapy efficacy and for the eradication of latent viral infections. We report here that limitation of essential amino acids, such as methionine and cysteine, causes selective up-regulation of exogenous transgene expression in mammalian cells. Prolonged amino acid deprivation led to significant and reversible increase in the expression levels of stably integrated transgenes transcribed by means of viral or human promoters in HeLa cells. This phenomenon was mediated by epigenetic chromatin modifications, because histone deacetylase (HDAC) inhibitors reproduced starvation-induced transgene up-regulation, and transcriptome analysis, ChIP, and pharmacological and RNAi approaches revealed that a specific class II HDAC, namely HDAC4, plays a critical role in maintaining the silencing of exogenous transgenes. This mechanism was also operational in cells chronically infected with HIV-1, the etiological agent of AIDS, in a latency state. Indeed, both amino acid starvation and pharmacological inhibition of HDAC4 promoted reactivation of HIV-1 transcription and reverse transcriptase activity production in HDAC4\n                    <jats:sup>+<\/jats:sup>\n                    ACH-2 T-lymphocytic cells but not in HDAC4\n                    <jats:sup>\u2212<\/jats:sup>\n                    U1 promonocytic cells. Thus, amino acid deprivation leads to transcriptional derepression of silenced transgenes, including integrated plasmids and retroviruses, by a process involving inactivation or down-regulation of HDAC4. These findings suggest that selective targeting of HDAC4 might represent a unique strategy for modulating the expression of therapeutic viral vectors, as well as that of integrated HIV-1 proviruses in latent reservoirs without significant cytotoxicity.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1202174109","type":"journal-article","created":{"date-parts":[[2012,7,24]],"date-time":"2012-07-24T00:48:19Z","timestamp":1343090899000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":38,"title":["Amino acid starvation induces reactivation of silenced transgenes and latent HIV-1 provirus via down-regulation of histone deacetylase 4 (HDAC4)"],"prefix":"10.1073","volume":"109","author":[{"given":"Ilaria","family":"Palmisano","sequence":"first","affiliation":[{"name":"Center for Translational Genomics and Bioinformatics, San Raffaele Scientific Institute, Ospedale San Raffaele, 20132 Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Della Chiara","sequence":"additional","affiliation":[{"name":"Division of Immunology, Transplantation, and Infectious Diseases, San Raffaele Scientific Institute, Ospedale San Raffaele, 20132 Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa Lucia","family":"D\u2019Ambrosio","sequence":"additional","affiliation":[{"name":"Center for Translational Genomics and Bioinformatics, San Raffaele Scientific Institute, Ospedale San Raffaele, 20132 Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Huichalaf","sequence":"additional","affiliation":[{"name":"Dulbecco Telethon Institute and Division of Regenerative Medicine, San Raffaele Scientific Institute, Ospedale San Raffaele, 20132 Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Brambilla","sequence":"additional","affiliation":[{"name":"Institute of Experimental Neurology and Division of Neuroscience, Department of Neurology, San Raffaele Scientific Institute, Ospedale San Raffaele, 20132 Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Corbetta","sequence":"additional","affiliation":[{"name":"Division of Immunology, Transplantation, and Infectious Diseases, San Raffaele Scientific Institute, Ospedale San Raffaele, 20132 Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Riba","sequence":"additional","affiliation":[{"name":"Center for Translational Genomics and Bioinformatics, San Raffaele Scientific Institute, Ospedale San Raffaele, 20132 Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosanna","family":"Piccirillo","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Valente","sequence":"additional","affiliation":[{"name":"Dipartimento di Chimica e Tecnologie del Farmaco, Istituto Pasteur\u2013Fondazione Cenci Bolognetti, Universit\u00e0 di Roma \u201cLa Sapienza,\u201d 00185 Roma, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Casari","sequence":"additional","affiliation":[{"name":"Center for Translational Genomics and Bioinformatics, San Raffaele Scientific Institute, Ospedale San Raffaele, 20132 Milan, Italy;"},{"name":"School of Medicine, Vita-Salute San Raffaele University, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonello","family":"Mai","sequence":"additional","affiliation":[{"name":"Dipartimento di Chimica e Tecnologie del Farmaco, Istituto Pasteur\u2013Fondazione Cenci Bolognetti, Universit\u00e0 di Roma \u201cLa Sapienza,\u201d 00185 Roma, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo Martinelli","family":"Boneschi","sequence":"additional","affiliation":[{"name":"Institute of Experimental Neurology and Division of Neuroscience, Department of Neurology, San Raffaele Scientific Institute, Ospedale San Raffaele, 20132 Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Gabellini","sequence":"additional","affiliation":[{"name":"Dulbecco Telethon Institute and Division of Regenerative Medicine, San Raffaele Scientific Institute, Ospedale San Raffaele, 20132 Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Poli","sequence":"additional","affiliation":[{"name":"Division of Immunology, Transplantation, and Infectious Diseases, San Raffaele Scientific Institute, Ospedale San Raffaele, 20132 Milan, Italy;"},{"name":"School of Medicine, Vita-Salute San Raffaele University, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Vittoria","family":"Schiaffino","sequence":"additional","affiliation":[{"name":"Center for Translational Genomics and Bioinformatics, San Raffaele Scientific Institute, Ospedale San Raffaele, 20132 Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,7,23]]},"reference":[{"key":"e_1_1_2_17_8_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2010.138"},{"key":"e_1_1_2_17_8_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1191047"},{"key":"e_1_1_2_17_8_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/COH.0b013e328341242d"},{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1146\/annurev.nutr.24.012003.132145","article-title":"Nutritional control of gene expression: How mammalian cells respond to amino acid limitation","volume":"25","author":"Kilberg MS","year":"2005","unstructured":"MS Kilberg, YX Pan, H Chen, V Leung-Pineda, Nutritional control of gene expression: How mammalian cells respond to amino acid limitation. Annu Rev Nutr 25, 59\u201385 (2005).","journal-title":"Annu Rev Nutr"},{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/nrg2752","article-title":"Chromatin structure and the inheritance of epigenetic information","volume":"11","author":"Margueron R","year":"2010","unstructured":"R Margueron, D Reinberg, Chromatin structure and the inheritance of epigenetic information. Nat Rev Genet 11, 285\u2013296 (2010).","journal-title":"Nat Rev Genet"},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1038\/nrg2485","article-title":"The many roles of histone deacetylases in development and physiology: Implications for disease and therapy","volume":"10","author":"Haberland M","year":"2009","unstructured":"M Haberland, RL Montgomery, EN Olson, The many roles of histone deacetylases in development and physiology: Implications for disease and therapy. Nat Rev Genet 10, 32\u201342 (2009).","journal-title":"Nat Rev Genet"},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"17335","DOI":"10.1073\/pnas.0706487104","article-title":"Unraveling the hidden catalytic activity of vertebrate class IIa histone deacetylases","volume":"104","author":"Lahm A","year":"2007","unstructured":"A Lahm, et al., Unraveling the hidden catalytic activity of vertebrate class IIa histone deacetylases. Proc Natl Acad Sci USA 104, 17335\u201317340 (2007).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/S1097-2765(01)00429-4","article-title":"Enzymatic activity associated with class II HDACs is dependent on a multiprotein complex containing HDAC3 and SMRT\/N-CoR","volume":"9","author":"Fischle W","year":"2002","unstructured":"W Fischle, et al., Enzymatic activity associated with class II HDACs is dependent on a multiprotein complex containing HDAC3 and SMRT\/N-CoR. Mol Cell 9, 45\u201357 (2002).","journal-title":"Mol Cell"},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"3958","DOI":"10.1158\/1078-0432.CCR-08-2785","article-title":"Clinical studies of histone deacetylase inhibitors","volume":"15","author":"Prince HM","year":"2009","unstructured":"HM Prince, MJ Bishton, SJ Harrison, Clinical studies of histone deacetylase inhibitors. Clin Cancer Res 15, 3958\u20133969 (2009).","journal-title":"Clin Cancer Res"},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"3940","DOI":"10.2174\/138161209789649349","article-title":"Histone deacetylase inhibitors and neurodegenerative disorders: Holding the promise","volume":"15","author":"Mai A","year":"2009","unstructured":"A Mai, D Rotili, S Valente, AG Kazantsev, Histone deacetylase inhibitors and neurodegenerative disorders: Holding the promise. Curr Pharm Des 15, 3940\u20133957 (2009).","journal-title":"Curr Pharm Des"},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.phrs.2010.02.014","article-title":"Histone deacetylase inhibitors: Keeping momentum for neuromuscular and cardiovascular diseases treatment","volume":"62","author":"Colussi C","year":"2010","unstructured":"C Colussi, et al., Histone deacetylase inhibitors: Keeping momentum for neuromuscular and cardiovascular diseases treatment. Pharmacol Res 62, 3\u201310 (2010).","journal-title":"Pharmacol Res"},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1097\/QAD.0b013e3283467041","article-title":"HIV cure and eradication: How will we get from the laboratory to effective clinical trials?","volume":"25","author":"Lewin SR","year":"2011","unstructured":"SR Lewin, C Rouzioux, HIV cure and eradication: How will we get from the laboratory to effective clinical trials? AIDS 25, 885\u2013897 (2011).","journal-title":"AIDS"},{"key":"e_1_3_4_10_2","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1097\/COH.0b013e3283412384","article-title":"Epigenetic regulation of HIV latency","volume":"6","author":"Hakre S","year":"2011","unstructured":"S Hakre, L Chavez, K Shirakawa, E Verdin, Epigenetic regulation of HIV latency. Curr Opin HIV AIDS 6, 19\u201324 (2011).","journal-title":"Curr Opin HIV AIDS"},{"key":"e_1_3_4_11_2","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1097\/COH.0b013e328341242d","article-title":"Histone deacetylase inhibitors and HIV latency","volume":"6","author":"Margolis DM","year":"2011","unstructured":"DM Margolis, Histone deacetylase inhibitors and HIV latency. Curr Opin HIV AIDS 6, 25\u201329 (2011).","journal-title":"Curr Opin HIV AIDS"},{"key":"e_1_3_4_12_2","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/12715","article-title":"Ocular albinism: Evidence for a defect in an intracellular signal transduction system","volume":"23","author":"Schiaffino MV","year":"1999","unstructured":"MV Schiaffino, et al., Ocular albinism: Evidence for a defect in an intracellular signal transduction system. Nat Genet 23, 108\u2013112 (1999).","journal-title":"Nat Genet"},{"key":"e_1_3_4_13_2","doi-asserted-by":"crossref","first-page":"e236","DOI":"10.1371\/journal.pbio.0060236","article-title":"L-DOPA is an endogenous ligand for OA1","volume":"6","author":"Lopez VM","year":"2008","unstructured":"VM Lopez, CL Decatur, WD Stamer, RM Lynch, BS McKay, L-DOPA is an endogenous ligand for OA1. PLoS Biol 6, e236 (2008).","journal-title":"PLoS Biol"},{"key":"e_1_3_4_14_2","doi-asserted-by":"crossref","first-page":"3589","DOI":"10.1242\/jcs.051011","article-title":"mTOR signaling at a glance","volume":"122","author":"Laplante M","year":"2009","unstructured":"M Laplante, DM Sabatini, mTOR signaling at a glance. J Cell Sci 122, 3589\u20133594 (2009).","journal-title":"J Cell Sci"},{"key":"e_1_3_4_15_2","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s10555-008-9118-y","article-title":"Demethylation of (Cytosine-5-C-methyl) DNA and regulation of transcription in the epigenetic pathways of cancer development","volume":"27","author":"Patra SK","year":"2008","unstructured":"SK Patra, A Patra, F Rizzi, TC Ghosh, S Bettuzzi, Demethylation of (Cytosine-5-C-methyl) DNA and regulation of transcription in the epigenetic pathways of cancer development. Cancer Metastasis Rev 27, 315\u2013334 (2008).","journal-title":"Cancer Metastasis Rev"},{"key":"e_1_3_4_16_2","doi-asserted-by":"crossref","first-page":"17174","DOI":"10.1016\/S0021-9258(17)44885-X","article-title":"Potent and specific inhibition of mammalian histone deacetylase both in vivo and in vitro by trichostatin A","volume":"265","author":"Yoshida M","year":"1990","unstructured":"M Yoshida, M Kijima, M Akita, T Beppu, Potent and specific inhibition of mammalian histone deacetylase both in vivo and in vitro by trichostatin A. J Biol Chem 265, 17174\u201317179 (1990).","journal-title":"J Biol Chem"},{"key":"e_1_3_4_17_2","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1093\/nar\/gkm1028","article-title":"CpG methylation plays a vital role in determining tissue- and cell-specific expression of the human cell-death-inducing DFF45-like effector A gene through the regulation of Sp1\/Sp3 binding","volume":"36","author":"Li D","year":"2008","unstructured":"D Li, L Da, H Tang, T Li, M Zhao, CpG methylation plays a vital role in determining tissue- and cell-specific expression of the human cell-death-inducing DFF45-like effector A gene through the regulation of Sp1\/Sp3 binding. Nucleic Acids Res 36, 330\u2013341 (2008).","journal-title":"Nucleic Acids Res"},{"key":"e_1_3_4_18_2","doi-asserted-by":"crossref","first-page":"3344","DOI":"10.1021\/jm049002a","article-title":"Class II (IIa)-selective histone deacetylase inhibitors. 1. Synthesis and biological evaluation of novel (aryloxopropenyl)pyrrolyl hydroxyamides","volume":"48","author":"Mai A","year":"2005","unstructured":"A Mai, et al., Class II (IIa)-selective histone deacetylase inhibitors. 1. Synthesis and biological evaluation of novel (aryloxopropenyl)pyrrolyl hydroxyamides. J Med Chem 48, 3344\u20133353 (2005).","journal-title":"J Med Chem"},{"key":"e_1_3_4_19_2","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1016\/j.bbapap.2009.09.030","article-title":"Regulation of yeast sirtuins by NAD(+) metabolism and calorie restriction","volume":"1804","author":"Lu SP","year":"2010","unstructured":"SP Lu, SJ Lin, Regulation of yeast sirtuins by NAD(+) metabolism and calorie restriction. Biochim Biophys Acta 1804, 1567\u20131575 (2010).","journal-title":"Biochim Biophys Acta"},{"key":"e_1_3_4_20_2","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/S0140-6736(05)67098-5","article-title":"Depletion of latent HIV-1 infection in vivo: A proof-of-concept study","volume":"366","author":"Lehrman G","year":"2005","unstructured":"G Lehrman, et al., Depletion of latent HIV-1 infection in vivo: A proof-of-concept study. Lancet 366, 549\u2013555 (2005).","journal-title":"Lancet"},{"key":"e_1_3_4_21_2","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1089\/aid.2008.0191","article-title":"Expression of latent HIV induced by the potent HDAC inhibitor suberoylanilide hydroxamic acid","volume":"25","author":"Archin NM","year":"2009","unstructured":"NM Archin, et al., Expression of latent HIV induced by the potent HDAC inhibitor suberoylanilide hydroxamic acid. AIDS Res Hum Retroviruses 25, 207\u2013212 (2009).","journal-title":"AIDS Res Hum Retroviruses"},{"key":"e_1_3_4_22_2","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.4049\/jimmunol.140.4.1117","article-title":"Characterization of a promonocyte clone chronically infected with HIV and inducible by 13-phorbol-12-myristate acetate","volume":"140","author":"Folks TM","year":"1988","unstructured":"TM Folks, et al., Characterization of a promonocyte clone chronically infected with HIV and inducible by 13-phorbol-12-myristate acetate. J Immunol 140, 1117\u20131122 (1988).","journal-title":"J Immunol"},{"key":"e_1_3_4_23_2","doi-asserted-by":"crossref","first-page":"431","DOI":"10.4049\/jimmunol.142.2.431","article-title":"Monokine regulation of human immunodeficiency virus-1 expression in a chronically infected human T cell clone","volume":"142","author":"Clouse KA","year":"1989","unstructured":"KA Clouse, et al., Monokine regulation of human immunodeficiency virus-1 expression in a chronically infected human T cell clone. J Immunol 142, 431\u2013438 (1989).","journal-title":"J Immunol"},{"key":"e_1_3_4_24_2","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1126\/science.2470148","article-title":"Interferon-alpha but not AZT suppresses HIV expression in chronically infected cell lines","volume":"244","author":"Poli G","year":"1989","unstructured":"G Poli, JM Orenstein, A Kinter, TM Folks, AS Fauci, Interferon-alpha but not AZT suppresses HIV expression in chronically infected cell lines. Science 244, 575\u2013577 (1989).","journal-title":"Science"},{"key":"e_1_3_4_25_2","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/1742-4690-6-52","article-title":"\u201cShock and kill\u201d effects of class I-selective histone deacetylase inhibitors in combination with the glutathione synthesis inhibitor buthionine sulfoximine in cell line models for HIV-1 quiescence","volume":"6","author":"Savarino A","year":"2009","unstructured":"A Savarino, et al., \u201cShock and kill\u201d effects of class I-selective histone deacetylase inhibitors in combination with the glutathione synthesis inhibitor buthionine sulfoximine in cell line models for HIV-1 quiescence. Retrovirology 6, 52 (2009).","journal-title":"Retrovirology"},{"key":"e_1_3_4_26_2","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/j.jmb.2011.03.044","article-title":"Negative regulation of HIV-1 transcription by a heterodimeric NF-\u03baB1\/p50 and C-terminally truncated STAT5 complex","volume":"410","author":"Della Chiara G","year":"2011","unstructured":"G Della Chiara, et al., Negative regulation of HIV-1 transcription by a heterodimeric NF-\u03baB1\/p50 and C-terminally truncated STAT5 complex. J Mol Biol 410, 933\u2013943 (2011).","journal-title":"J Mol Biol"},{"key":"e_1_3_4_27_2","doi-asserted-by":"crossref","first-page":"6785","DOI":"10.1158\/0008-5472.CAN-05-4563","article-title":"Inhibition of histone deacetylase class I but not class II is critical for the sensitization of leukemic cells to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis","volume":"66","author":"Inoue S","year":"2006","unstructured":"S Inoue, A Mai, MJ Dyer, GM Cohen, Inhibition of histone deacetylase class I but not class II is critical for the sensitization of leukemic cells to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis. Cancer Res 66, 6785\u20136792 (2006).","journal-title":"Cancer Res"},{"key":"e_1_3_4_28_2","volume-title":"Retroviruses","author":"Brown PO","year":"1997","unstructured":"PO Brown, Integration. Retroviruses, eds JM Coffin, SH Hughes, HE Varmus (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 1997)."},{"key":"e_1_3_4_29_2","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/gt.2010.138","article-title":"Physiological and tissue-specific vectors for treatment of inherited diseases","volume":"18","author":"Toscano MG","year":"2011","unstructured":"MG Toscano, et al., Physiological and tissue-specific vectors for treatment of inherited diseases. Gene Ther 18, 117\u2013127 (2011).","journal-title":"Gene Ther"},{"key":"e_1_3_4_30_2","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1126\/science.1191047","article-title":"HIV persistence and the prospect of long-term drug-free remissions for HIV-infected individuals","volume":"329","author":"Trono D","year":"2010","unstructured":"D Trono, et al., HIV persistence and the prospect of long-term drug-free remissions for HIV-infected individuals. Science 329, 174\u2013180 (2010).","journal-title":"Science"},{"key":"e_1_3_4_31_2","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.cell.2004.10.024","article-title":"Histone deacetylase 4 controls chondrocyte hypertrophy during skeletogenesis","volume":"119","author":"Vega RB","year":"2004","unstructured":"RB Vega, et al., Histone deacetylase 4 controls chondrocyte hypertrophy during skeletogenesis. Cell 119, 555\u2013566 (2004).","journal-title":"Cell"},{"key":"e_1_3_4_32_2","doi-asserted-by":"crossref","first-page":"33752","DOI":"10.1074\/jbc.M706268200","article-title":"The histone deacetylase HDAC4 connects neural activity to muscle transcriptional reprogramming","volume":"282","author":"Cohen TJ","year":"2007","unstructured":"TJ Cohen, et al., The histone deacetylase HDAC4 connects neural activity to muscle transcriptional reprogramming. J Biol Chem 282, 33752\u201333759 (2007).","journal-title":"J Biol Chem"},{"key":"e_1_3_4_33_2","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1083\/jcb.201101046","article-title":"Modulation of chromatin position and gene expression by HDAC4 interaction with nucleoporins","volume":"193","author":"Kehat I","year":"2011","unstructured":"I Kehat, F Accornero, BJ Aronow, JD Molkentin, Modulation of chromatin position and gene expression by HDAC4 interaction with nucleoporins. J Cell Biol 193, 21\u201329 (2011).","journal-title":"J Cell Biol"},{"key":"e_1_3_4_34_2","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1126\/science.6189183","article-title":"Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS)","volume":"220","author":"Barr\u00e9-Sinoussi F","year":"1983","unstructured":"F Barr\u00e9-Sinoussi, et al., Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 220, 868\u2013871 (1983).","journal-title":"Science"},{"key":"e_1_3_4_35_2","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1126\/science.6200935","article-title":"Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS","volume":"224","author":"Popovic M","year":"1984","unstructured":"M Popovic, MG Sarngadharan, E Read, RC Gallo, Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science 224, 497\u2013500 (1984).","journal-title":"Science"},{"key":"e_1_3_4_36_2","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1126\/science.278.5341.1295","article-title":"Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy","volume":"278","author":"Finzi D","year":"1997","unstructured":"D Finzi, et al., Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science 278, 1295\u20131300 (1997).","journal-title":"Science"},{"key":"e_1_3_4_37_2","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1126\/science.1165706","article-title":"The challenge of finding a cure for HIV infection","volume":"323","author":"Richman DD","year":"2009","unstructured":"DD Richman, et al., The challenge of finding a cure for HIV infection. Science 323, 1304\u20131307 (2009).","journal-title":"Science"},{"key":"e_1_3_4_38_2","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1016\/j.bcp.2004.05.040","article-title":"Administration of HDAC inhibitors to reactivate HIV-1 expression in latent cellular reservoirs: Implications for the development of therapeutic strategies","volume":"68","author":"Demont\u00e9 D","year":"2004","unstructured":"D Demont\u00e9, V Quivy, Y Colette, C Van Lint, Administration of HDAC inhibitors to reactivate HIV-1 expression in latent cellular reservoirs: Implications for the development of therapeutic strategies. Biochem Pharmacol 68, 1231\u20131238 (2004).","journal-title":"Biochem Pharmacol"},{"key":"e_1_3_4_39_2","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1097\/QAD.0b013e328333bfa1","article-title":"Novel histone deacetylase inhibitors CG05 and CG06 effectively reactivate latently infected HIV-1","volume":"24","author":"Choi BS","year":"2010","unstructured":"BS Choi, et al., Novel histone deacetylase inhibitors CG05 and CG06 effectively reactivate latently infected HIV-1. AIDS 24, 609\u2013611 (2010).","journal-title":"AIDS"},{"key":"e_1_3_4_40_2","doi-asserted-by":"crossref","first-page":"e6093","DOI":"10.1371\/journal.pone.0006093","article-title":"Synergistic activation of HIV-1 expression by deacetylase inhibitors and prostratin: Implications for treatment of latent infection","volume":"4","author":"Reuse S","year":"2009","unstructured":"S Reuse, et al., Synergistic activation of HIV-1 expression by deacetylase inhibitors and prostratin: Implications for treatment of latent infection. PLoS ONE 4, e6093 (2009).","journal-title":"PLoS ONE"},{"key":"e_1_3_4_41_2","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1186\/1743-422X-7-266","article-title":"Cell line-dependent variability in HIV activation employing DNMT inhibitors","volume":"7","author":"Fernandez G","year":"2010","unstructured":"G Fernandez, SL Zeichner, Cell line-dependent variability in HIV activation employing DNMT inhibitors. Virol J 7, 266 (2010).","journal-title":"Virol J"},{"key":"e_1_3_4_42_2","doi-asserted-by":"crossref","first-page":"12039","DOI":"10.1128\/JVI.00396-10","article-title":"Histone deacetylases and the nuclear receptor corepressor regulate lytic-latent switch gene 50 in murine gammaherpesvirus 68-infected macrophages","volume":"84","author":"Goodwin MM","year":"2010","unstructured":"MM Goodwin, et al., Histone deacetylases and the nuclear receptor corepressor regulate lytic-latent switch gene 50 in murine gammaherpesvirus 68-infected macrophages. J Virol 84, 12039\u201312047 (2010).","journal-title":"J Virol"},{"key":"e_1_3_4_43_2","doi-asserted-by":"crossref","first-page":"4370","DOI":"10.1021\/jm8002894","article-title":"Use of the nitrile oxide cycloaddition (NOC) reaction for molecular probe generation: A new class of enzyme selective histone deacetylase inhibitors (HDACIs) showing picomolar activity at HDAC6","volume":"51","author":"Kozikowski AP","year":"2008","unstructured":"AP Kozikowski, S Tapadar, DN Luchini, KH Kim, DD Billadeau, Use of the nitrile oxide cycloaddition (NOC) reaction for molecular probe generation: A new class of enzyme selective histone deacetylase inhibitors (HDACIs) showing picomolar activity at HDAC6. J Med Chem 51, 4370\u20134373 (2008).","journal-title":"J Med Chem"},{"key":"e_1_3_4_44_2","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1242\/jcs.02930","article-title":"An unconventional dileucine-based motif and a novel cytosolic motif are required for the lysosomal and melanosomal targeting of OA1","volume":"119","author":"Piccirillo R","year":"2006","unstructured":"R Piccirillo, et al., An unconventional dileucine-based motif and a novel cytosolic motif are required for the lysosomal and melanosomal targeting of OA1. J Cell Sci 119, 2003\u20132014 (2006).","journal-title":"J Cell Sci"},{"key":"e_1_3_4_45_2","doi-asserted-by":"crossref","first-page":"3487","DOI":"10.1093\/hmg\/ddn241","article-title":"The ocular albinism type 1 protein, an intracellular G protein-coupled receptor, regulates melanosome transport in pigment cells","volume":"17","author":"Palmisano I","year":"2008","unstructured":"I Palmisano, et al., The ocular albinism type 1 protein, an intracellular G protein-coupled receptor, regulates melanosome transport in pigment cells. Hum Mol Genet 17, 3487\u20133501 (2008).","journal-title":"Hum Mol Genet"},{"key":"e_1_3_4_46_2","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/onc.2008.371","article-title":"HDAC4 represses p21(WAF1\/Cip1) expression in human cancer cells through a Sp1-dependent, p53-independent mechanism","volume":"28","author":"Mottet D","year":"2009","unstructured":"D Mottet, et al., HDAC4 represses p21(WAF1\/Cip1) expression in human cancer cells through a Sp1-dependent, p53-independent mechanism. Oncogene 28, 243\u2013256 (2009).","journal-title":"Oncogene"},{"key":"e_1_3_4_47_2","doi-asserted-by":"crossref","first-page":"9055","DOI":"10.1073\/pnas.93.17.9055","article-title":"The ocular albinism type 1 gene product is a membrane glycoprotein localized to melanosomes","volume":"93","author":"Schiaffino MV","year":"1996","unstructured":"MV Schiaffino, et al., The ocular albinism type 1 gene product is a membrane glycoprotein localized to melanosomes. Proc Natl Acad Sci USA 93, 9055\u20139060 (1996).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_48_2","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak KJ","year":"2001","unstructured":"KJ Livak, TD Schmittgen, Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25, 402\u2013408 (2001).","journal-title":"Methods"},{"key":"e_1_3_4_49_2","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1093\/nar\/29.9.e45","article-title":"A new mathematical model for relative quantification in real-time RT-PCR","volume":"29","author":"Pfaffl MW","year":"2001","unstructured":"MW Pfaffl, A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29, e45 (2001).","journal-title":"Nucleic Acids Res"},{"key":"e_1_3_4_50_2","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1038\/nprot.2006.98","article-title":"Chromatin immunoprecipitation and microarray-based analysis of protein location","volume":"1","author":"Lee TI","year":"2006","unstructured":"TI Lee, SE Johnstone, RA Young, Chromatin immunoprecipitation and microarray-based analysis of protein location. Nat Protoc 1, 729\u2013748 (2006).","journal-title":"Nat Protoc"},{"key":"e_1_3_4_51_2","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/sj.emboj.7601516","article-title":"Recruitment of chromatin-modifying enzymes by CTIP2 promotes HIV-1 transcriptional silencing","volume":"26","author":"Marban C","year":"2007","unstructured":"C Marban, et al., Recruitment of chromatin-modifying enzymes by CTIP2 promotes HIV-1 transcriptional silencing. EMBO J 26, 412\u2013423 (2007).","journal-title":"EMBO J"},{"key":"e_1_3_4_52_2","doi-asserted-by":"crossref","first-page":"6550","DOI":"10.1093\/emboj\/cdg631","article-title":"Regulation of HIV-1 gene expression by histone acetylation and factor recruitment at the LTR promoter","volume":"22","author":"Lusic M","year":"2003","unstructured":"M Lusic, A Marcello, A Cereseto, M Giacca, Regulation of HIV-1 gene expression by histone acetylation and factor recruitment at the LTR promoter. EMBO J 22, 6550\u20136561 (2003).","journal-title":"EMBO J"},{"key":"e_1_3_4_53_2","doi-asserted-by":"crossref","first-page":"7515","DOI":"10.1128\/JVI.73.9.7515-7523.1999","article-title":"Envelope-dependent restriction of human immunodeficiency virus type 1 spreading in CD4(+) T lymphocytes: R5 but not X4 viruses replicate in the absence of T-cell receptor restimulation","volume":"73","author":"Vicenzi E","year":"1999","unstructured":"E Vicenzi, et al., Envelope-dependent restriction of human immunodeficiency virus type 1 spreading in CD4(+) T lymphocytes: R5 but not X4 viruses replicate in the absence of T-cell receptor restimulation. J Virol 73, 7515\u20137523 (1999).","journal-title":"J Virol"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1202174109","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,24]],"date-time":"2023-06-24T12:36:16Z","timestamp":1687610176000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1202174109"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,7,23]]},"references-count":56,"journal-issue":{"issue":"34","published-print":{"date-parts":[[2012,8,21]]}},"alternative-id":["10.1073\/pnas.1202174109"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1202174109","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,7,23]]},"assertion":[{"value":"2012-07-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}