|
|
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.
 Previous Article | Next Article 
Submitted January 23, 2007
Accepted April 3, 2007
Developmental and differentiation-specific patterns of human  and  -globin promoter DNA methylation
Rodwell H. Mabaera, Christine A. Richardson, Kristen J. Johnson, Mei Hsu, Steven H. Fiering, and Christopher H. Lowrey*
Department of Pharmacology & Toxicology, Dartmouth Medical School, Lebanon, NH, United States
Department of Medicine, Dartmouth Medical School, Lebanon, NH, United States
Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH, United States
Department of Genetics, Dartmouth Medical School, Lebanon, NH, United States
* Corresponding author; email: c.lowrey{at}dartmouth.edu.
The mechanisms underlying the human fetal to adult  -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 non-human systems. We have evaluated human  and -globin promoter methylation in primary human fetal liver (FL) and adult 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 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 pre-erythroid phase of differentiation and are then re-methylated 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 -globin promoter methylation and support the hypothesis that promoter methylation plays a key role in human -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]
|
|
|
|
|
