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Binding patterns of BCL11A in the globin and GATA1 loci and characterization of the BCL11A fetal hemoglobin locus

Kiran Jawaid, Karin Wahlberg, Swee Lay Thein, and Steve Best

Blood Cells Mol Dis 45(2):7 (2010) PMID 20542454

BCL11A is a major regulator of fetal hemoglobin production. Reduced levels of BCL11A have been shown to delay switching from fetal to adult hemoglobin, suggesting that it acts as a stage-specific repressor of @c globin expression. We have carried out a survey of BCL11A binding in the globin, BCL11A and GATA1 loci by ChIP-on-chip analysis in primary human erythroid cells. We found strong occupancy in both @a and @b globin upstream regulatory regions as well as in regions involved in switching and hereditary persistence of fetal hemoglobin. Genetic studies have identified a restricted 14kb region in BCL11A intron 2 as being highly associated with HbF levels. Strong GATA-1 binding and acetylated histone H3 was found in this area, which could be indicative of a regulatory element, changes in which might be responsible for the overall regulation of BCL11A. We also observed BCL11A and GATA-1 binding in a known auto-regulatory promoter element of the GATA1 locus.

Copyright © 2010 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.bcmd.2010.05.006
Version: za2963e q8za3 q8zbc q8zcc q8zd3 q8ze2 q8zfd q8zg2
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