A physiological delay in human fetal hemoglobin switching is associated with specific globin DNA hypomethylation

FEBS Letters

Faller, Douglas V.¹  Greene, Michael F.¹  Perrine, Susan P.¹  Cohen, Ruth A.¹ 

[1] Bruce Lyon Memorial Research Laboratory, Children's Hospital Medical Center, Oakland, CA, USA

关键词: DNA hypomethylation;    Gene expression;    Globin gene;   

DOI  :  10.1016/0014-5793(88)80603-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The human fetal-to-adult globin switch normally occurs on a fixed schedule, beginning at 32–34 weeks gestation, and recent studies have suggested an association between this developmental inactivation of the fetal (γ) globin genes and the appearance of methylation within and around these genes. We have studied a population of infants in whom this switch does not occur before birth (infants of diabetic mothers, IDM) and examined the patterns of methylation surrounding their active γ-globin genes, in comparison to the γ-globin genes of age-matched controls who have switched their pattern of globin gene expression on schedule. All genomic DNA samples from infants with delays in the globin switch demonstrated extensive hypomethylation in the region of the γ-globin genes, comparable to that found in the genomes of fetuses of less than 21 weeks gestation. DNA from the erythroid cells of infants of 32–40 weeks gestation had no detectable hypomethylation in the γ-globin region. These findings support the concept that hypomethylation is an accurate developmental marker of globin gene switching, and suggest that globin gene expression in IDM may be arrested at an early preswitch stage.

【 授权许可】

Unknown