REVIEW: Genetic and Epigenetic Mechanisms of β-Globin Gene Switching

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O. V. Iarovaia^1,2*, A. P. Kovina^1,2,3, N. V. Petrova^1,2, S. V. Razin^1,2,3, E. S. Ioudinkova^1,2, Y. S. Vassetzky^2,4, and S. V. Ulianov^1,2,3

¹Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia; E-mail: iarovaia@inbox.ru

²French–Russian Laboratory for Research in Oncology LIA1066, Russia–France

³Lomonosov Moscow State University, Biological Faculty, 119991 Moscow, Russia

⁴Institut Gustave Roussy, 39 rue Camille-Desmoulins, 94805 Villejuif, France

^* To whom correspondence should be addressed.

Received November 20, 2017; Revision received December 8, 2017

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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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KEY WORDS: α- and β-globin genes domains, hemoglobin switching, transcriptional regulation, spatial organization of chromatin

DOI: 10.1134/S0006297918040090

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