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 language | English (US) |
|---|---|
| Title of host publication | Annals of the New York Academy of Sciences |
| Pages | 64-68 |
| Number of pages | 5 |
| Volume | 1202 |
| DOIs | |
| State | Published - Aug 2010 |
Publication series
| Name | Annals of the New York Academy of Sciences |
|---|---|
| Volume | 1202 |
| ISSN (Print) | 00778923 |
| ISSN (Electronic) | 17496632 |
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Keywords
- BCL11A
- fetal hemoglobin
- globin switching
- thalassemia
- transcription
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
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 proceeding › Conference contribution
}
TY - GEN
T1 - Transcriptional silencing of fetal hemoglobin by BCL11A
AU - Sankaran, Vijay G.
AU - Xu, Jian
AU - Orkin, Stuart H.
PY - 2010/8
Y1 - 2010/8
N2 - 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.
AB - 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.
KW - BCL11A
KW - fetal hemoglobin
KW - globin switching
KW - thalassemia
KW - transcription
UR - http://www.scopus.com/inward/record.url?scp=77955866470&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77955866470&partnerID=8YFLogxK
U2 - 10.1111/j.1749-6632.2010.05574.x
DO - 10.1111/j.1749-6632.2010.05574.x
M3 - Conference contribution
C2 - 20712774
AN - SCOPUS:77955866470
SN - 9781573317825
VL - 1202
T3 - Annals of the New York Academy of Sciences
SP - 64
EP - 68
BT - Annals of the New York Academy of Sciences
ER -