Advanced

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

Jawaid, Kiran; Wahlberg, Karin LU ; Thein, Swee Lay and Best, Steve (2010) In Blood Cells, Molecules & Diseases 45(2). p.6-140
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,... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
publishing date
type
Contribution to journal
publication status
published
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
in
Blood Cells, Molecules & Diseases
volume
45
issue
2
pages
6 - 140
publisher
Elsevier
external identifiers
  • scopus:77955271206
ISSN
1096-0961
DOI
10.1016/j.bcmd.2010.05.006
language
English
LU publication?
no
id
1720cd92-55e4-4fbf-8e9b-d15d8494b26d
date added to LUP
2017-10-25 11:08:04
date last changed
2018-10-07 05:01:26
@article{1720cd92-55e4-4fbf-8e9b-d15d8494b26d,
  abstract     = {<p>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.</p>},
  author       = {Jawaid, Kiran and Wahlberg, Karin and Thein, Swee Lay and Best, Steve},
  issn         = {1096-0961},
  keyword      = {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},
  language     = {eng},
  month        = {08},
  number       = {2},
  pages        = {6--140},
  publisher    = {Elsevier},
  series       = {Blood Cells, Molecules & Diseases},
  title        = {Binding patterns of BCL11A in the globin and GATA1 loci and characterization of the BCL11A fetal hemoglobin locus},
  url          = {http://dx.doi.org/10.1016/j.bcmd.2010.05.006},
  volume       = {45},
  year         = {2010},
}