Understanding globin regulation in β-thalassemia: it’s as simple as α, β, γ, δ
Arthur Bank
Arthur Bank
Published June 1, 2005
Citation Information: J Clin Invest. 2005;115(6):1470-1473. https://doi.org/10.1172/JCI25398.
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Commentary

Understanding globin regulation in β-thalassemia: it’s as simple as α, β, γ, δ

Abstract

A vast excess of α-globin production and inadequate γ-globin compensation lead to the development of severe anemia in human β-thalassemia. Newly identified modifiers of α- and γ-globin synthesis and insights into the mechanisms of globin regulation provide the tools for potential new approaches to treating this and other red blood cell disorders. In the study by Han and colleagues in this issue of the JCI, the activity of a heme-regulated protein, HRI, is shown to modulate the accumulation of excess α-globin chains in murine β-thalassemia and to decrease the severity of the disease.

Authors

Arthur Bank

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A model for human γ-to-β globin switching and γ-globin reactivation in a...
A model for human γ-to-β globin switching and γ-globin reactivation in adult hematopoietic cells. In fetal life, the human γ-globin genes are preferentially activated by interactions between the β-LCR and the γ-globin genes mediated by transcription factors and chromatin remodeling complexes. The details of these complexes at this time are unknown. In adult-type hematopoietic cells, chromatin remodeling complexes repress γ-globin transcription, change the conformation of the β-globin locus by binding to the intergenic γ_δ sequences, and favor interactions between the β-LCR and the downstream β-globin gene. PYR complex, shown here binding to the region upstream of the human δ-globin gene (and included in the Corfu deletion) with Ikaros as its DNA-binding subunit, is a known adult erythroid stage_specific chromatin remodeling complex that may function in this process. The subunits of PYR complex are shown. These include SWI/SNF subunits, parts of an ATP-generated chromatin remodeling complex that activate gene transcription; NURD subunits, parts of a repressive chromatin remodeling complex with HDACs; and Ikaros as the DNA-binding subunit that holds the complex together (11).