Transcriptional silencing of fetal hemoglobin by BCL11A

Vijay G. Sankaran, Jian Xu, Stuart H. Orkin

Research output: Chapter in Book/Report/Conference proceedingConference contribution

28 Citations (Scopus)

Abstract

The β-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 γ-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 γ-globin gene silencing, BCL11A should be considered as a therapeutic target to increase HbF in a directed manner in β-thalassemia patients.

Original languageEnglish (US)
Title of host publicationAnnals of the New York Academy of Sciences
Pages64-68
Number of pages5
Volume1202
DOIs
StatePublished - Aug 2010

Publication series

NameAnnals of the New York Academy of Sciences
Volume1202
ISSN (Print)00778923
ISSN (Electronic)17496632

Fingerprint

Fetal Hemoglobin
Globins
Thalassemia
Genes
Switch Genes
Erythroid Cells
Switches
Gene Silencing
Mammals
Hemoglobins
Medical problems
Population
Therapeutics

Keywords

  • BCL11A
  • fetal hemoglobin
  • globin switching
  • thalassemia
  • transcription

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Sankaran, V. G., Xu, J., & Orkin, S. H. (2010). Transcriptional silencing of fetal hemoglobin by BCL11A. In Annals of the New York Academy of Sciences (Vol. 1202, pp. 64-68). (Annals of the New York Academy of Sciences; Vol. 1202). https://doi.org/10.1111/j.1749-6632.2010.05574.x

Transcriptional silencing of fetal hemoglobin by BCL11A. / Sankaran, Vijay G.; Xu, Jian; Orkin, Stuart H.

Annals of the New York Academy of Sciences. Vol. 1202 2010. p. 64-68 (Annals of the New York Academy of Sciences; Vol. 1202).

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Sankaran, VG, Xu, J & Orkin, SH 2010, Transcriptional silencing of fetal hemoglobin by BCL11A. in Annals of the New York Academy of Sciences. vol. 1202, Annals of the New York Academy of Sciences, vol. 1202, pp. 64-68. https://doi.org/10.1111/j.1749-6632.2010.05574.x
Sankaran VG, Xu J, Orkin SH. Transcriptional silencing of fetal hemoglobin by BCL11A. In Annals of the New York Academy of Sciences. Vol. 1202. 2010. p. 64-68. (Annals of the New York Academy of Sciences). https://doi.org/10.1111/j.1749-6632.2010.05574.x
Sankaran, Vijay G. ; Xu, Jian ; Orkin, Stuart H. / Transcriptional silencing of fetal hemoglobin by BCL11A. Annals of the New York Academy of Sciences. Vol. 1202 2010. pp. 64-68 (Annals of the New York Academy of Sciences).
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