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Blood, 15 September 2006, Vol. 108, No. 6, pp. 2081-2086. Prepublished online as a Blood First Edition Paper on May 30, 2006; DOI 10.1182/blood-2006-04-015859. This Article Full Text Full Text (PDF) Supplemental Table All Versions of this Article: blood-2006-04-015859v1 108/6/2081    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Oneal, P. A. Articles by Miller, J. L. Search for Related Content PubMed PubMed Citation Articles by Oneal, P. A. Articles by Miller, J. L. Related Collections Red Cells Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Fetal hemoglobin silencing in humans Patricia A. Oneal, Nicole M. Gantt, Joseph D. Schwartz, Natarajan V. Bhanu, Y. Terry Lee, John W. Moroney, Christopher H. Reed, Alan N. Schechter, Naomi L. C. Luban, and Jeffery L. Miller From the Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD; the National Naval Medical Center, Department of Obstetrics and Gynecology, Bethesda, MD; and Laboratory Medicine and Pathology, Children's National Medical Center, Washington, DC. Interruption of the normal fetal-to-adult transition of hemoglobin expression should largely ameliorate sickle cell and beta-thalassemia syndromes. Achievement of this clinical goal requires a robust understanding of gamma-globin gene and protein silencing during human development. For this purpose, age-related changes in globin phenotypes of circulating human erythroid cells were examined from 5 umbilical cords, 99 infants, and 5 adult donors. Unexpectedly, an average of 95% of the cord blood erythrocytes and reticulocytes expressed HbA and the adult beta-globin gene, as well as HbF and the gamma-globin genes. The distribution of hemoglobin and globin gene expression then changed abruptly due to the expansion of cells lacking HbF or gamma-globin mRNA (silenced cells). In adult reticulocytes, less than 5% expressed gamma-globin mRNA. These data are consistent with a "switching" model in humans that initially results largely from gamma- and beta-globin gene coexpression and competition during fetal development. In contrast, early postnatal life is marked by the rapid accumulation of cells that possess undetectable gamma-globin mRNA and HbF. The silencing phenomenon is mediated by a mechanism of cellular replacement. This novel silencing pattern may be important for the development of HbF-enhancing therapies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Dijon, F. Bardin, A. Murati, M. Batoz, C. Chabannon, and C. Tonnelle The role of Ikaros in human erythroid differentiation Blood, February 1, 2008; 111(3): 1138 - 1146. [Abstract] [Full Text] [PDF] S.-H. Goh, M. Josleyn, Y. T. Lee, R. L. Danner, R. B. Gherman, M. C. Cam, and J. L. Miller The human reticulocyte transcriptome Physiol Genomics, July 18, 2007; 30(2): 172 - 178. [Abstract] [Full Text] [PDF] E. Coleman and B. Inusa Sickle Cell Anemia: Targeting the Role of Fetal Hemoglobin in Therapy Clinical Pediatrics, June 1, 2007; 46(5): 386 - 391. [Abstract] [PDF]

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