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Blood, 15 April 2006, Vol. 107, No. 8, pp. 3359-3370. Prepublished online as a Blood First Edition Paper on December 27, 2005; DOI 10.1182/blood-2005-07-2888. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-07-2888v1 107/8/3359    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hodge, D. Articles by Perkins, A. Search for Related Content PubMed PubMed Citation Articles by Hodge, D. Articles by Perkins, A. Related Collections Hemostasis, Thrombosis, and Vascular Biology Red Cells Cytoskeleton Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS A global role for EKLF in definitive and primitive erythropoiesis Denise Hodge, Elise Coghill, Janelle Keys, Tina Maguire, Belinda Hartmann, Alasdair McDowall, Mitchell Weiss, Sean Grimmond, and Andrew Perkins From the Institute for Molecular Biosciences and the Australian Special Research Centre for Functional and Applied Genomics, University of Queensland, Brisbane, Australia; and The Children's Hospital of Philadelphia and the University of Pennsylvania, Philadelphia. Erythroid Kruppel-like factor (EKLF, KLF1) plays an important role in definitive erythropoiesis and -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 included -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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. K. Singleton, N. M. Burton, C. Green, R. L. Brady, and D. J. Anstee Mutations in EKLF/KLF1 form the molecular basis of the rare blood group In(Lu) phenotype Blood, September 1, 2008; 112(5): 2081 - 2088. [Abstract] [Full Text] [PDF] T. Yokomizo, K. Hasegawa, H. Ishitobi, M. Osato, M. Ema, Y. Ito, M. Yamamoto, and S. Takahashi Runx1 is involved in primitive erythropoiesis in the mouse Blood, April 15, 2008; 111(8): 4075 - 4080. [Abstract] [Full Text] [PDF] I. Bruns, U. Steidl, J. C. Fischer, A. Czibere, G. Kobbe, S. Raschke, R. Singh, R. Fenk, M. Rosskopf, S. Pechtel, et al. Pegylated granulocyte colony-stimulating factor mobilizes CD34+ cells with different stem and progenitor subsets and distinct functional properties in comparison with unconjugated granulocyte colony-stimulating factor Haematologica, March 1, 2008; 93(3): 347 - 355. [Abstract] [Full Text] [PDF] M. Siatecka, L. Xue, and J. J. Bieker Sumoylation of EKLF Promotes Transcriptional Repression and Is Involved in Inhibition of Megakaryopoiesis Mol. Cell. Biol., December 15, 2007; 27(24): 8547 - 8560. [Abstract] [Full Text] [PDF] P. Basu, T. K. Lung, W. Lemsaddek, T. G. Sargent, D. C. Williams Jr, M. Basu, L. C. Redmond, J. B Lingrel, J. L. Haar, and J. A. Lloyd EKLF and KLF2 have compensatory roles in embryonic {beta}-globin gene expression and primitive erythropoiesis Blood, November 1, 2007; 110(9): 3417 - 3425. [Abstract] [Full Text] [PDF] A. P. W. Funnell, C. A. Maloney, L. J. Thompson, J. Keys, M. Tallack, A. C. Perkins, and M. Crossley Erythroid Kruppel-Like Factor Directly Activates the Basic Kruppel-Like Factor Gene in Erythroid Cells Mol. Cell. Biol., April 1, 2007; 27(7): 2777 - 2790. [Abstract] [Full Text] [PDF] Y.-C. Shyu, T.-L. Lee, S.-C. Wen, H. Chen, W.-Y. Hsiao, X. Chen, J. Hwang, and C.-K. J. Shen Subcellular Transport of EKLF and Switch-On of Murine Adult {beta}maj Globin Gene Transcription Mol. Cell. Biol., March 15, 2007; 27(6): 2309 - 2323. [Abstract] [Full Text] [PDF] M. Rokushima, K. Omi, A. Araki, Y. Kyokawa, N. Furukawa, F. Itoh, K. Imura, K. Takeuchi, M. Okada, I. Kato, et al. A Toxicogenomic Approach Revealed Hepatic Gene Expression Changes Mechanistically Linked to Drug-Induced Hemolytic Anemia Toxicol. Sci., February 1, 2007; 95(2): 474 - 484. [Abstract] [Full Text] [PDF] S. Hosoya-Ohmura, N. Mochizuki, M. Suzuki, O. Ohneda, K. Ohneda, and M. Yamamoto GATA-4 Incompletely Substitutes for GATA-1 in Promoting Both Primitive and Definitive Erythropoiesis in Vivo J. Biol. 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