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; Steve Best

doi:10.1016/j.bcmd.2010.05.006

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, Steve Best

King's College London

Research output: Contribution to journal › Article › peer-review

54 Citations (Scopus)

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 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.

Original language	English
Pages (from-to)	140 - 146
Number of pages	7
Journal	Blood Cells Molecules and Diseases
Volume	45
Issue number	2
DOIs	https://doi.org/10.1016/j.bcmd.2010.05.006
Publication status	Published - Aug 2010

Access to Document

10.1016/j.bcmd.2010.05.006

Cite this

@article{ce08d856190e4f44b7d176992b2c5658,

title = "Binding patterns of BCL11A in the globin and GATA1 loci and characterization of the BCL11A fetal hemoglobin locus",

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 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.",

author = "Kiran Jawaid and Karin Wahlberg and Thein, {Swee Lay} and Steve Best",

year = "2010",

month = aug,

doi = "10.1016/j.bcmd.2010.05.006",

language = "English",

volume = "45",

pages = "140 -- 146",

journal = "Blood Cells Molecules and Diseases",

publisher = "ACADEMIC PRESS INC",

number = "2",

}

TY - JOUR

T1 - Binding patterns of BCL11A in the globin and GATA1 loci and characterization of the BCL11A fetal hemoglobin locus

AU - Jawaid, Kiran

AU - Wahlberg, Karin

AU - Thein, Swee Lay

AU - Best, Steve

PY - 2010/8

Y1 - 2010/8

N2 - 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.

AB - 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.

U2 - 10.1016/j.bcmd.2010.05.006

DO - 10.1016/j.bcmd.2010.05.006

M3 - Article

VL - 45

SP - 140

EP - 146

JO - Blood Cells Molecules and Diseases

JF - Blood Cells Molecules and Diseases

IS - 2

ER -

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

Abstract

Access to Document

Fingerprint

Cite this