Genetic and Epigenetic Mechanisms of β-Globin Gene Switching
Biochemistry (Moscow)(2018)
摘要
Vertebrates have multiple forms of hemoglobin that differ in the composition of their polypeptide chains. During ontogenesis, the composition of these subunits changes. Genes encoding different α- and β-polypeptide chains are located in two multigene clusters on different chromosomes. Each cluster contains several genes that are expressed at different stages of ontogenesis. The phenomenon of stage-specific transcription of globin genes is referred to as globin gene switching. Mechanisms of expression switching, stage-specific activation, and repression of transcription of α- and β-globin genes are of interest from both theoretical and practical points of view. Alteration of balanced expression of globin genes, which usually occurs due to damage to adult β-globin genes, leads to development of severe diseases–hemoglobinopathies. In most cases, reactivation of the fetal hemoglobin gene in patients with β-thalassemia and sickle cell disease can reduce negative consequences of irreversible alterations of expression of the β-globin genes. This review focuses on the current state of research on genetic and epigenetic mechanisms underlying stage-specific switching of β-globin genes.
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关键词
α- and β-globin genes domains,hemoglobin switching,transcriptional regulation,spatial organization of chromatin
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