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Blood, 1 January 2005, Vol. 105, No. 1, pp. 387-393. Prepublished online as a Blood First Edition Paper on September 14, 2004; DOI 10.1182/blood-2004-04-1599. This Article Full Text (PDF) All Versions of this Article: 2004-04-1599v1 105/1/387    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Bhanu, N. V Articles by Miller, J. L Search for Related Content PubMed PubMed Citation Articles by Bhanu, N. V Articles by Miller, J. L Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 5, 2004 Accepted August 20, 2004 A sustained and pancellular reversal of gamma-globin gene silencing in adult human erythroid precursor cells Natarajan V Bhanu, Tiffany A Trice, Y Terry Lee, Nicole Gantt, Patricia Oneal, Joseph D Schwartz, Pierre Noel, and Jeffery L Miller* Laboratory of Chemical Biology, National Institute of Health, Bethesda, MD, USA; NIDDK and Hematology Services, Dept. of Laboratory Medicine, National Institute of Health, Bethesda, MD, USA Laboratory of Chemical Biology, National Institute of Health, Bethesda, MD, USA * Corresponding author; email: jm7f{at}nih.gov. We systematically compared cytokine-mediated increases or decreases in proliferation with globin gene and protein expression in adult human erythroblasts. Despite their opposite effects on growth, stem cell factor (SCF) and transforming growth factor-beta (TGF-B) had synergistic effects with respect to HbF: average HbF/HbF+HbA ratio in erythropoietin (EPO)=1.4±1.0%; EPO+TGF-B=10.8±1.9%; EPO+SCF=19.1±6.2%; EPO+SCF+TGF-B (EST)=39.3±6.3%. PCR revealed significant increases in gamma-globin transcripts that were balanced by reduced beta-globin transcripts. Single-cell quantitative PCR demonstrated a complete reversal of gamma-globin gene silencing with detectable gamma-globin mRNA in over 95% of the cells. Immunostaining with HbF antibodies also showed a pancellular distribution in EST (96.2±0.01% HbF-positive) compared with a heterocellular distribution in EPO (42.9±0.01% HbF-positive). As shown here for the first time, a robust and pancellular reversal of gamma-globin gene silencing among hemoglobinized erythroblasts from adult humans may be achieved in the absence of hereditary mutation or direct genomic manipulation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: O. Sripichai, C. M. Kiefer, N. V. Bhanu, T. Tanno, S.-J. Noh, S.-H. Goh, J. E. Russell, C. L. Rognerud, C.-N. Ou, P. A. Oneal, et al. Cytokine-mediated increases in fetal hemoglobin are associated with globin gene histone modification and transcription factor reprogramming Blood, September 10, 2009; 114(11): 2299 - 2306. [Abstract] [Full Text] [PDF] W. Aerbajinai, J. Zhu, C. Kumkhaek, K. Chin, and G. P. Rodgers SCF induces {gamma}-globin gene expression by regulating downstream transcription factor COUP-TFII Blood, July 2, 2009; 114(1): 187 - 194. [Abstract] [Full Text] [PDF] R. Mabaera, M. R. Greene, C. A. Richardson, S. J. Conine, C. D. Kozul, and C. H. Lowrey Neither DNA hypomethylation nor changes in the kinetics of erythroid differentiation explain 5-azacytidine's ability to induce human fetal hemoglobin Blood, January 1, 2008; 111(1): 411 - 420. 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Thein cMYB is involved in the regulation of fetal hemoglobin production in adults Blood, August 1, 2006; 108(3): 1077 - 1083. [Abstract] [Full Text] [PDF] N. V. Bhanu, Y. T. Lee, P. A. Oneal, C. L. Rognerud, C.-N. Ou, and J. L. Miller Silencing Reversed: Coordinated Expression of Embryonic and Fetal Globin Genes in Adult Human Erythroblasts. Blood (ASH Annual Meeting Abstracts), November 16, 2005; 106(11): 821 - 821. [Abstract]

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