A global role for EKLF in definitive and primitive erythropoiesis

Hodge, Denise, Coghill, Elise, Keys, Janelle, Maguire, Tina, Hartmann, Belinda, McDowall, Alasdair, Weiss, Mitchell, Grimmond, Sean and Perkins, Andrew (2006) A global role for EKLF in definitive and primitive erythropoiesis. Blood, 107 8: 3359-3370.


Author Hodge, Denise
Coghill, Elise
Keys, Janelle
Maguire, Tina
Hartmann, Belinda
McDowall, Alasdair
Weiss, Mitchell
Grimmond, Sean
Perkins, Andrew
Title A global role for EKLF in definitive and primitive erythropoiesis
Journal name Blood  (ERA 2012 Listed)    (ERA 2010 Rank A*)   Check publisher's open access policy
Publication date 2006
Sub-type Article
DOI 10.1182/blood-2005-07-2888
Volume number 107
Issue number 8
ISSN 0006-4971
Start page 3359
End page 3370
Total pages 12
Place of publication Washington
Publisher American Society of Hematology
Collection year 2006
Language eng
Subject C1
270201 Gene Expression
730103 Blood disorders
Abstract Erythroid Kruppel-like factor (EKLF, KLF1) plays an important role in definitive erythropoiesis and p-globin gene regulation but failure to rectify lethal fetal anemia upon correction of globin chain imbalance suggested additional critical EKLF target genes. We employed expression profiling of EKLF-null fetal liver and EKLF-null erythroid cell lines containing an inducible EKLF-estrogen receptor (EKLF-ER) fusion construct to search for such targets. An overlapping list of EKLF-regulated genes from the 2 systems in- cluded alpha-hemoglobin stabilizing protein (AHSP), cytoskeletal proteins, hemesynthesis enzymes, transcription factors, and blood group antigens. One EKLF target gene, dematin, which encodes an erythrocyte cytoskeletal protein (band 4.9), contains several phylogenetically conserved consensus CACC motifs predicted to bind EKLF. Chromatin immunoprecipitation demonstrated in vivo EKLF occupancy at these sites and promoter reporter assays showed that EKLF activates gene transcription through these DNA elements. Furthermore, investigation of EKLF target genes in the yolk sac led to the discovery of unexpected additional defects in the embryonic red cell membrane and cytoskeleton. In short, EKLF regulates global erythroid gene expression that is critical for the development of primitive and definitive red cells.
Keyword Hematology
Kruppel-like Factor
Transcription Factor Gata-1
5-aminolevulinate Synthase Gene
Porphobilinogen Deaminase Gene
Box-binding-protein
Beta-thalassemia
Gamma-globin
Sideroblastic Anemia
Histone Acetylation
Regulatory Elements
Q-Index Code C1

Document type: Journal Article
Sub-type: Article
Collections: 2007 Higher Education Research Data Collection
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Created: Wed, 15 Aug 2007, 08:17:46 EST