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PMID: 15923635 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The erythroid phenotype of EKLF-null mice: defects in hemoglobin metabolism and membrane stability.

Molecular and cellular biology ·Vol. 25 ·No. 12 ·2005-06-00 ·Pages 5205-14

Drissen R, von Lindern M, Kolbus A, Driegen S, Steinlein P, Beug H, Grosveld F, Philipsen S

Abstract

Development of red blood cells requires the correct regulation of cellular processes including changes in cell morphology, globin expression and heme synthesis. Transcription factors such as erythroid Kruppel-like factor EKLF (Klf1) play a critical role in erythropoiesis. Mice lacking EKLF die around embryonic day 14 because of defective definitive erythropoiesis, partly caused by a deficit in beta-globin expression. To identify additional target genes, we analyzed the phenotype and gene expression profiles of wild-type and EKLF null primary erythroid progenitors that were differentiated synchronously in vitro. We show that EKLF is dispensable for expansion of erythroid progenitors, but required for the last steps of erythroid differentiation. We identify EKLF-dependent genes involved in hemoglobin metabolism and membrane stability. Strikingly, expression of these genes is also EKLF-dependent in primitive, yolk sac-derived, blood cells. Consistent with lack of upregulation of these genes we find previously undetected morphological abnormalities in EKLF-null primitive cells. Our data provide an explanation for the hitherto unexplained severity of the EKLF null phenotype in erythropoiesis.

MeSH Terms
Animals Antineoplastic Agents, Hormonal/metabolism Blood Proteins/genetics,metabolism Cell Differentiation/physiology Cell Membrane/metabolism Cytoskeletal Proteins DNA-Binding Proteins/genetics,metabolism Erythrocytes/cytology,physiology Erythropoiesis/physiology Gene Expression Profiling Gene Expression Regulation Hemoglobins/metabolism Kruppel-Like Transcription Factors Mice Mice, Knockout Molecular Chaperones/genetics,metabolism Oligonucleotide Array Sequence Analysis Phenotype Phosphoproteins/genetics,metabolism Recombinant Fusion Proteins/genetics,metabolism Tamoxifen/metabolism Transcription Factors/genetics,metabolism
Chemicals
Antineoplastic Agents, Hormonal Blood Proteins Cytoskeletal Proteins DNA-Binding Proteins Dmtn protein, mouse Hemoglobins Kruppel-Like Transcription Factors Molecular Chaperones Phosphoproteins Recombinant Fusion Proteins Transcription Factors erythroid Kruppel-like factor Tamoxifen
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Drissen Roy
Erasmus MC, Department of Cell Biology, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands.
von Lindern Marieke
Kolbus Andrea
Driegen Siska
Steinlein Peter
Beug Hartmut
Grosveld Frank
Philipsen Sjaak
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.25.12.5205-5214.2005
Published
2005-06-00
Pages
5205-14
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC1140573
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.25.12.5205-5214.2005 PMC Full Text View journal details
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