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Molecular and Cellular Biology, July 2007, p. 5047-5054, Vol. 27, No. 13
0270-7306/07/$08.00+0     doi:10.1128/MCB.02234-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

CpG Hypomethylation in a Large Domain Encompassing the Embryonic ß-Like Globin Genes in Primitive Erythrocytes{triangledown} ,{dagger}

Mei Hsu,1 Rodwell Mabaera,2 Christopher H. Lowrey,2 David I. K. Martin,3 and Steven Fiering1*

Department of Microbiology and Immunology, Department of Genetics, and Norris Cotton Cancer Center, Dartmouth Medical School, Hanover, New Hampshire,1 Department of Medicine, Department of Pharmacology and Toxicology, and Norris Cotton Cancer Center, Dartmouth Medical School, Hanover, New Hampshire,2 Children's Hospital Oakland Research Institute, Oakland, California3

Received 28 November 2006/ Returned for modification 22 January 2007/ Accepted 12 April 2007

There is little evidence addressing the role of CpG methylation in transcriptional control of genes that do not contain CpG islands. This is reflected in the ongoing debate about whether CpG methylation merely suppresses retroelements or if it also plays a role in developmental and tissue-specific gene regulation. The genes of the ß-globin locus are an important model of mammalian developmental gene regulation and do not contain CpG islands. We have analyzed the methylation status of regions in the murine ß-like globin locus in uncultured primitive and definitive erythroblasts and other cultured primary and transformed cell types. A large (~20-kb) domain is hypomethylated only in primitive erythroid cells; it extends from the region just past the locus control region to before ß-major and encompasses the embryonic genes Ey, ßh1, and ßh0. Even retrotransposons in this region are hypomethylated in primitive erythroid cells. The existence of this large developmentally regulated domain of hypomethylation supports a mechanistic role for DNA methylation in developmental regulation of globin genes.


* Corresponding author. Mailing address: Dartmouth Medical School, 6 Rubin, Dartmouth Hitchcock Medical Center, Lebanon, NH 03756. Phone: (603) 653-9966. Fax: (603) 653-9952. E-mail: fiering{at}dartmouth.edu

{triangledown} Published ahead of print on 23 April 2007.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.


Molecular and Cellular Biology, July 2007, p. 5047-5054, Vol. 27, No. 13
0270-7306/07/$08.00+0     doi:10.1128/MCB.02234-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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