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 C. (2006) A global role for EKLF in definitive and primitive erythropoiesis. Blood, 107 8: 3359-3370. doi:10.1182/blood-2005-07-2888


Author Hodge, Denise
Coghill, Elise
Keys, Janelle
Maguire, Tina
Hartmann, Belinda
McDowall, Alasdair
Weiss, Mitchell
Grimmond, Sean
Perkins, Andrew C.
Title A global role for EKLF in definitive and primitive erythropoiesis
Journal name Blood   Check publisher's open access policy
ISSN 0006-4971
1528-0020
Publication date 2006-04-15
Sub-type Article (original research)
DOI 10.1182/blood-2005-07-2888
Volume 107
Issue 8
Start page 3359
End page 3370
Total pages 12
Place of publication Washington, DC, United States
Publisher American Society of Hematology
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
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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Created: Wed, 07 Apr 2010, 13:22:59 EST by Laura McTaggart on behalf of Institute for Molecular Bioscience