Abstract
Haematopoiesisis the process of progenitor cell proliferation, differentiation, and maturation. Its control is mediated by growth factors (glycoproteins) and membrane receptors which, when activated, modify gene expression and patterns of differentiation. The erythroid pathway results in mature red blood cells; its haemoglobin (Hb) synthesis is possible because of a selective expression of the globin genes and a stability of the appropriate mRNAs. During the first few weeks of gestation, erythroblasts in the yolk sac produce the embryonic Gower Hbs (I = ζ 2 ε 2; II = α 2 ε 2) and Portland Hbs (I = ζ 2 γ 2; II = ζ 2 β 2; III = ζ 2 δ 2). At 10 weeks these Hb types are replaced by fetal Hbs (α 2 G γ 2; α 2 A γ 2) which are synthesized in definitive erythroblasts in the liver. Before birth a switch to Hb synthesis in the bone marrow occurs; these erythroblasts are committed to the synthesis of Hb A (α 2 β 2) and Hb A2 (α 2 δ 2). Thus, this complex process concerns a) mechanisms of cell differentiation, i.e. from the pluripotent stem cell to the erythroid cell line; b) activation of specific globin genes which, moreover, are expressed in different cell types; c) the mechanism(s) responsible for the formation of the extremely high levels of these proteins. Differential globin gene activation and regulation will be the major topic to be reviewed here. It should also be known that in non-erythroid cells the α and β clusters exist in chromatin structures which prevent digestion with DNase I, while the more open configuration in erythroid cells makes digestion possible.
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Huisman, T.H.J. (1995). Globin Gene Regulation. In: Sibinga, C.T.S., Das, P.C., Briët, E. (eds) Hereditary Diseases and Blood Transfusion. Developments in Hematology and Immunology, vol 30. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2017-7_5
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DOI: https://doi.org/10.1007/978-1-4615-2017-7_5
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