Human Fetal Hemoglobin Expression Is Regulated by the Developmental Stage-Specific Repressor BCL11A
Broad Institute · Boston Children's Hospital · +4 more institutions
Abstract
Differences in the amount of fetal hemoglobin (HbF) that persists into adulthood affect the severity of sickle cell disease and the beta-thalassemia syndromes. Genetic association studies have identified sequence variants in the gene BCL11A that influence HbF levels. Here, we examine BCL11A as a potential regulator of HbF expression. The high-HbF BCL11A genotype is associated with reduced BCL11A expression. Moreover, abundant expression of full-length forms of BCL11A is developmentally restricted to adult erythroid cells. Down-regulation of BCL11A expression in primary adult erythroid cells leads to robust HbF expression. Consistent with a direct role of BCL11A in globin gene regulation, we find that BCL11A…
Citation impact
- FWCI
- 18.04
- Percentile
- 100%
- References
- 27
Authors
10- VGVijay G. Sankaran
Broad Institute, Boston Children's Hospital, Harvard University, University of California, Los Angeles, Dana-Farber Cancer Institute, Harvard Stem Cell Institute
- TMTobias Menne
Broad Institute, Boston Children's Hospital, Harvard University, University of California, Los Angeles, Dana-Farber Cancer Institute, Harvard Stem Cell Institute
- JXJian Xu
Broad Institute, Boston Children's Hospital, Harvard University, University of California, Los Angeles, Dana-Farber Cancer Institute, Harvard Stem Cell Institute
- TEThomas E. Akie
Broad Institute, Boston Children's Hospital, Harvard University, University of California, Los Angeles, Dana-Farber Cancer Institute, Harvard Stem Cell Institute
- GLGuillaume Lettre
Broad Institute, Boston Children's Hospital, Harvard University, University of California, Los Angeles, Dana-Farber Cancer Institute, Harvard Stem Cell Institute
Topics & keywords
- Fetal hemoglobin
- Repressor
- Hemoglobin
- Fetus
- Biology
- Developmental stage
- Expression (computer science)
- Developmental biology
- Good health and well-being