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

Research output: Contribution to journalArticle

Abstract

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 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.

Details

Authors
External organisations
  • King's College London
Research areas and keywords

Keywords

  • Carrier Proteins, Erythroid Cells, Fetal Hemoglobin, GATA1 Transcription Factor, Gene Expression Regulation, Genetic Loci, Hemoglobinopathies, Histones, Humans, K562 Cells, Nuclear Proteins, Regulatory Elements, Transcriptional, Journal Article, Research Support, Non-U.S. Gov't
Original languageEnglish
Pages (from-to)140-6
JournalBlood Cells, Molecules & Diseases
Volume45
Issue number2
Publication statusPublished - 2010 Aug 15
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes