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Transcriptional silencing of fetal hemoglobin by BCL11A

Vijay G Sankaran1, Jian Xu, Stuart H Orkin

  • 1Division of Hematology/Oncology, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA.

Annals of the New York Academy of Sciences
|August 18, 2010
PubMed

The beta-thalassemia syndromes are a major global health problem. Increased levels of fetal hemoglobin (HbF) ameliorate the clinical symptoms seen in this disease. By taking advantage of the natural variation in the level of HbF in various populations, we and others identified several common genetic variants in three major loci that regulate HbF levels. One of these variants resides in the gene BCL11A. We have studied the role of this gene product and established that BCL11A maintains silencing of gamma-globin expression in adult erythroid cells and functions as a direct transcriptional regulator of the fetal to adult hemoglobin switch in humans. Moreover, we found that BCL11A plays a central role in the evolutionarily divergent globin gene switches of mammals. As a factor critical for gamma-globin gene silencing, BCL11A should be considered as a therapeutic target to increase HbF in a directed manner in beta-thalassemia patients.

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