Learning about genomics and disease from the anucleate human red blood cell
Edward J. Benz Jr.
Edward J. Benz Jr.
Published November 22, 2010
Citation Information: J Clin Invest. 2010;120(12):4204-4206. https://doi.org/10.1172/JCI45433.
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Commentary

Learning about genomics and disease from the anucleate human red blood cell

Abstract

During the differentiation of an erythrocyte, the developing erythroblast shuts down expression of most of its genes but preserves high levels of expression of certain key genes, such as those encoding hemoglobin and critical membrane proteins. In this issue of the JCI, Gallagher et al. show that a specialized type of DNA sequence element known as an insulator protects the expression of ankyrin, a key membrane protein. In several kindreds, mutations in the insulator led to impaired ankyrin expression and congenital hemolytic anemia. This work provides important insights into ways in which epigenetic changes can alter gene expression and thereby lead to human disease.

Authors

Edward J. Benz Jr.

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Figure 1

Basic structure of the erythrocyte membrane and cytoskeleton.

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Basic structure of the erythrocyte membrane and cytoskeleton. The diagra...
The diagram shows that the membrane is composed of a lipid bilayer punctuated by transmembrane proteins including Band3 and glycophorin C (GPC). The erythrocyte gains its strength and flexibility from the underlying cytoskeleton, which consists primarily of α- and β-spectrin. Spectrin (α- and β-spectrin) is attached flexibly to the membrane via ankyrin, which binds to Band 3, and via protein 4.1, which binds GPC. The other proteins shown enhance the strength of the binding. “Vertical interactions” provide strong attachments of the cytoskeleton to the lipid bilayer. “Horizontal interactions” allow the cell to stretch reversibly under shear stress without fragmentation. CaM, calmodulin; 4.1R80, 80-kDa erythrocyte isoform of protein 4.1R. Figure adapted from Frontiers in Bioscience (2).