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

被引：51

作者：

Jawaid, Kiran ^{[1
]}

Wahlberg, Karin ^{[1
]}

Thein, Swee Lay ^{[1
]}

Best, Steve ^{[1
]}

机构：

[1] Kings Coll London, James Black Ctr, London SE5 9NU, England

来源：

BLOOD CELLS MOLECULES AND DISEASES | 2010年 / 45卷 / 02期

基金：

英国医学研究理事会;

关键词：

BCL11A; GATA1; HbF; ChIP; Hemoglobinopathies; GENOME-WIDE ASSOCIATION; SICKLE-CELL-DISEASE; BETA-THALASSEMIA; ERYTHROID-CELLS; GENE-EXPRESSION; INTERGENIC TRANSCRIPTION; HEREDITARY PERSISTENCE; REGULATORY REGION; DNA-BINDING; COMPLEX;

D O I：

10.1016/j.bcmd.2010.05.006

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 gamma 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 alpha and beta globin upstream regulatory regions as well as in regions involved in switching and hereditary persistence of fetal hemoglobin. Genetic studies have identified a restricted 14 kb 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. (C) 2010 Elsevier Inc. All rights reserved.

引用

页码：140 / 146

页数：7

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