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The Hemoglobin Regulatory Regions

  • Betty S. PaceEmail author
  • Levi H. Makala
Chapter

Abstract

All animals that use hemoglobin for oxygen transport synthesize different hemoglobin types during the various stages of development. In humans, two gene clusters direct the production of hemoglobin including the α-locus which contains the embryonic ζ gene and two adult α genes on chromosome 16. A second cluster, the β-globin locus located on chromosome 11, contains the ε, Gγ, Aγ, δ, and β genes. The globin genes are arranged from 5′ to 3′ according to the order of their expression and are developmentally regulated to produce different hemoglobin species during ontogeny. Two switches in the type of hemoglobin synthesized during development occur, a process known as hemoglobin switching. Through research efforts over the last two decades, several insights have been gained into the molecular mechanisms of hemoglobin switching. However, the entire process has not been fully elucidated. Studies of naturally occurring globin gene promoter mutations and transgenic mouse investigations have contributed to our understanding of the effect of DNA mutations on globin gene expression. Furthermore, the developmental regulation of globin gene expression has shaped research efforts to establish therapeutic modalities for individuals affected with sickle cell disease and β-thalassemia. Here, we will review the progress made toward understanding molecular mechanisms that control globin gene expression and the consequences of mutations on hemoglobin switching.

Keywords

Hemoglobin ε-Globin γ-Globin β-Globin α-Globin Hereditary persistence of fetal hemoglobin Hemoglobin switching Thalassemia Sickle cell disease 

Abbreviations

CDP

CCAAT displacement protein

CBP

CREB-binding protein

DRED

Direct repeat erythroid-definitive

Hb F

Fetal hemoglobin

HPFH

Hereditary persistence of fetal hemoglobin

HS

Hypersensitive site

LCR

Locus control region

SSE

Stage selector element

SSP

Stage selector protein

STAT3

Signal transducers and activators of transcription

Hb SS

Sickle cell anemia

SCD

Sickle cell disease

SNP

Single nucleotide polymorphism

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© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Georgia’s Health Sciences UniversityAugustaUSA

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