Increasing haemoglobin β-chain synthesis in foetal development is associated with a declining γ- to α-mRNA ratio

Haig H. Kazazian, Arthur M. Silverstein, Pamela G. Snyder, Rebecca J. Vanbeneden    

Research output: Contribution to journalArticle

Abstract

DURING human foetal development, the predominant haemoglobin in erythrocytes switches twice (Fig. 1). First, ε chains of embryonic haemoglobins in erythroblasts of yolk sac origin are replaced by γ chains of foetal haemoglobin and traces of β chains of adult haemoglobin. This switch occurs very early in foetal development, coincident with the appearance of a new type of peripheral erythrocyte of hepatic origin. Second, at about 32 weeks of gestation, predominantly γ-chain production gives way to increased β-chain synthesis within a constant cell type1. This double haemoglobin switch also occurs in other animals, including sheep 2. Not only is very little known about the biological basis for the switch from γ- to β-chain production, but the basic changes in gene activity involved in the switching process are obscure. An understanding of the γ to β switch has clinical importance, for if one could block the switch and increase γ-chain production, sickle cell anaemia and β-thalassaemia could be treated effectively. We present here data concerning changes in globin gene activity, as assessed by globin mRNA levels, which are temporally related to the turning up of β-chain synthesis. These observations were originally made in erythroid cells of aborted human foetuses and were extended to cells from foetal sheep.

Original languageEnglish (US)
Pages (from-to)67-70
Number of pages4
JournalNature
Volume260
Issue number5546
DOIs
StatePublished - Dec 1 1976

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