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Blood, 15 August 2007, Vol. 110, No. 4, pp. 1343-1352. Prepublished online as a Blood First Edition Paper on April 24, 2007; DOI 10.1182/blood-2007-01-068635. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-01-068635v1 110/4/1343    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 Mabaera, R. Articles by Lowrey, C. H. Search for Related Content PubMed PubMed Citation Articles by Mabaera, R. Articles by Lowrey, C. H. Related Collections Red Cells Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Developmental- and differentiation-specific patterns of human - and ß-globin promoter DNA methylation Rodwell Mabaera1,5, Christine A. Richardson2,5, Kristin Johnson2,5, Mei Hsu3,5, Steven Fiering3,5, and Christopher H. Lowrey1,2,5 Departments of1 Pharmacology and Toxicology 2 Medicine 3 Microbiology and Immunology, and 4 Genetics of Dartmouth Medical School, Hanover, NH; and the 5 Norris Cotton Cancer Center of Dartmouth-Hitchcock Medical Center, Lebanon, NH The mechanisms underlying the human fetal-to-adult ß-globin gene switch remain to be determined. While there is substantial experimental evidence to suggest that promoter DNA methylation is involved in this process, most data come from studies in nonhuman systems. We have evaluated human - and ß-globin promoter methylation in primary human fetal liver (FL) and adult bone marrow (ABM) erythroid cells. Our results show that, in general, promoter methylation and gene expression are inversely related. However, CpGs at –162 of the promoter and –126 of the ß promoter are hypomethylated in ABM and FL, respectively. We also studied -globin promoter methylation during in vitro differentiation of erythroid cells. The promoters are initially hypermethylated in CD34+ cells. The upstream promoter CpGs become hypomethylated during the preerythroid phase of differentiation and are then remethylated later, during erythropoiesis. The period of promoter hypomethylation correlates with transient -globin gene expression and may explain the previously observed fetal hemoglobin production that occurs during early adult erythropoiesis. These results provide the first comprehensive survey of developmental changes in human - and ß-globin promoter methylation and support the hypothesis that promoter methylation plays a role in human ß-globin locus gene switching. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Harju-Baker, F. C. Costa, H. Fedosyuk, R. Neades, and K. R. Peterson Silencing of A{gamma}-Globin Gene Expression during Adult Definitive Erythropoiesis Mediated by GATA-1-FOG-1-Mi2 Complex Binding at the -566 GATA Site Mol. Cell. Biol., May 15, 2008; 28(10): 3101 - 3113. [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. [Abstract] [Full Text] [PDF] W. Yin, G. Barkess, X. Fang, P. Xiang, H. Cao, G. Stamatoyannopoulos, and Q. Li Histone acetylation at the human {beta}-globin locus changes with developmental age Blood, December 1, 2007; 110(12): 4101 - 4107. [Abstract] [Full Text] [PDF]

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