Teamwork between 2 key proteins necessary for normal development and regulation of red blood cells

RICHMOND, Va. (Aug. 6, 2007) Virginia Commonwealth University researchers studying hemoglobin genes, mutations of which play a role in genetic blood disorders like sickle cell anemia and beta-thalassemia, have identified two proteins that are responsible for regulating overlapping groups of genes during the development of red blood cells.

The findings may point researchers to future gene therapies for patients with sickle cell anemia and beta-thalassemia.

In an article pre-published online Aug. 3 as a First Edition Paper in the journal Blood, the journal of the American Association for Hematology, researchers reported that a protein called KLF2 coordinates with a related and well-studied transcription factor, EKLF, in the regulation of embryonic globin genes responsible for the development of mouse embryonic red blood cells.

EKLF plays a central role in the developmental regulation of the adult beta-globin gene, and is essential for the maturation and stability of adult red blood cells. KLF2 is a protein crucial for making embryonic red blood cells.

If EKLF and KLF2 can turn on the embryonic globin genes in adult cells we don't know if this is true yet - then these findings may provide a gene therapy approach for treating sickle cell anemia and beta-thalassemia. It is well-established that the expression of embryonic globin genes can help ameliorate these diseases, said Joyce A. Lloyd, Ph.D., associate professor of human genetics at the VCU Massey Cancer Center, and corresponding author for this study.

Lloyds team studied gene expression and red blood cell development in the mouse embryo. They used mouse embryos missing both the KLF2 and EKLF genes to show that embryonic globin expression is severely reduced, and that the embryos therefore are anemic, compared to mice missing KLF2 or EKLF alone.

This likely means that EKLF and KLF2, which are related transcription factors, regulate overlapping grou

Contact: Sathya Achia-Abraham
Virginia Commonwealth University

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