SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on February 6, 2003; DOI 10.1182/blood-2002-09-2708. This Article Full Text (PDF) All Versions of this Article: 2002-09-2708v1 101/11/4333    most recent Alert me when this article is cited Alert me if a correction is posted 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 Elagib, K. E Articles by Goldfarb, A. N Search for Related Content PubMed PubMed Citation Articles by Elagib, K. E Articles by Goldfarb, A. N Social Bookmarking                   What's this? Submitted September 4, 2002 Accepted January 23, 2003 RUNX1 and GATA-1 coexpression and cooperation in megakaryocytic differentiation Kamaleldin E Elagib, Frederick K Racke, Michael Mogass, Rina Khetawat, Lorrie L Delehanty, and Adam N Goldfarb* Department of Pathology, University of Virginia, Charlottesville, VA, USA Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA * Corresponding author; email: ang3x{at}virginia.edu. Megakaryocytic and erythroid lineages derive from a common bipotential progenitor and share many transcription factors in common, most prominently factors of the GATA zinc finger family. Little is known about transcription factors unique to the megakaryocytic lineage that might program divergence from the erythroid pathway. To identify such factors, we employed the K562 system in which megakaryocyte lineage commitment is dependent on sustained ERK activation and is inhibited by stromal cell contact. During megakaryocytic induction in this system, the myeloid transcription factor RUNX1 underwent upregulation, dependent on ERK signaling and inhibitable by stromal cell contact. Immunostaining of normal human bone marrow confirmed strong expression of RUNX1 and cofactor CBF in megakaryocytes and minimal expression in erythroblasts. In primary human hematopoietic progenitor cultures, RUNX1 and CBF upregulation preceded megakaryocytic differentiation, and downregulation of these factors preceded erythroid differentiation. Functional studies showed cooperation among RUNX1, CBF and GATA-1 in the activation of a megakaryocytic promoter. By contrast, the RUNX1-ETO leukemic fusion protein potently repressed GATA-1 mediated transactivation. These functional interactions correlated with physical interactions observed between GATA-1 and RUNX1 factors. Enforced RUNX1 expression in K562 cells enhanced the induction of the megakaryocytic integrin proteins IIb and 2. These results suggest that RUNX1 may participate in programming of megakaryocytic lineage commitment through functional and physical interaction with GATA transcription factors. By contrast, RUNX1-ETO inhibition of GATA function may constitute a potential mechanism for the blockade of erythroid and megakaryocytic differentiation seen in leukemias with t(8;21). CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. K. Sims and J. C. Rice PR-Set7 Establishes a Repressive trans-Tail Histone Code That Regulates Differentiation Mol. Cell. Biol., July 15, 2008; 28(14): 4459 - 4468. [Abstract] [Full Text] [PDF] A. J. Woo, T. B. Moran, Y. L. Schindler, S.-K. Choe, N. B. Langer, M. R. Sullivan, Y. Fujiwara, B. H. Paw, and A. B. Cantor Identification of ZBP-89 as a Novel GATA-1-Associated Transcription Factor Involved in Megakaryocytic and Erythroid Development Mol. Cell. Biol., April 15, 2008; 28(8): 2675 - 2689. [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] L. Gutierrez, S. Tsukamoto, M. Suzuki, H. Yamamoto-Mukai, M. Yamamoto, S. Philipsen, and K. Ohneda Ablation of Gata1 in adult mice results in aplastic crisis, revealing its essential role in steady-state and stress erythropoiesis Blood, April 15, 2008; 111(8): 4375 - 4385. [Abstract] [Full Text] [PDF] L. Gilles, R. Guieze, D. Bluteau, V. Cordette-Lagarde, C. Lacout, R. Favier, F. Larbret, N. Debili, W. Vainchenker, and H. Raslova P19INK4D links endomitotic arrest and megakaryocyte maturation and is regulated by AML-1 Blood, April 15, 2008; 111(8): 4081 - 4091. [Abstract] [Full Text] [PDF] X. Zhao, V. Jankovic, A. Gural, G. Huang, A. Pardanani, S. Menendez, J. Zhang, R. Dunne, A. Xiao, H. Erdjument-Bromage, et al. Methylation of RUNX1 by PRMT1 abrogates SIN3A binding and potentiates its transcriptional activity Genes & Dev., March 1, 2008; 22(5): 640 - 653. [Abstract] [Full Text] [PDF] L. Zhang, F. B. Fried, H. Guo, and A. D. Friedman Cyclin-dependent kinase phosphorylation of RUNX1/AML1 on 3 sites increases transactivation potency and stimulates cell proliferation Blood, February 1, 2008; 111(3): 1193 - 1200. [Abstract] [Full Text] [PDF] J. A. Horsfield, S. H. Anagnostou, J. K.-H. Hu, K. H. Y. Cho, R. Geisler, G. Lieschke, K. E. Crosier, and P. S. Crosier Cohesin-dependent regulation of Runx genes Development, July 15, 2007; 134(14): 2639 - 2649. [Abstract] [Full Text] [PDF] A. G. Muntean, L. Pang, M. Poncz, S. F. Dowdy, G. A. Blobel, and J. D. Crispino Cyclin D-Cdk4 is regulated by GATA-1 and required for megakaryocyte growth and polyploidization Blood, June 15, 2007; 109(12): 5199 - 5207. [Abstract] [Full Text] [PDF] N. Asou, M. Yanagida, L. Huang, M. Yamamoto, K. Shigesada, H. Mitsuya, Y. Ito, and M. Osato Concurrent transcriptional deregulation of AML1/RUNX1 and GATA factors by the AML1-TRPS1 chimeric gene in t(8;21)(q24;q22) acute myeloid leukemia Blood, May 1, 2007; 109(9): 4023 - 4027. [Abstract] [Full Text] [PDF] J. Cammenga, B. Niebuhr, S. Horn, U. Bergholz, G. Putz, F. Buchholz, J. Lohler, and C. Stocking RUNX1 DNA-Binding Mutants, Associated with Minimally Differentiated Acute Myelogenous Leukemia, Disrupt Myeloid Differentiation Cancer Res., January 15, 2007; 67(2): 537 - 545. [Abstract] [Full Text] [PDF] B. Guyot, K. Murai, Y. Fujiwara, V. Valverde-Garduno, M. Hammett, S. Wells, N. Dear, S. H. Orkin, C. Porcher, and P. Vyas Characterization of a Megakaryocyte-specific Enhancer of the Key Hemopoietic Transcription Factor GATA1 J. Biol. Chem., May 12, 2006; 281(19): 13733 - 13742. [Abstract] [Full Text] [PDF] V. Hamelin, C. Letourneux, P.-H. Romeo, F. Porteu, and M. Gaudry Thrombopoietin regulates IEX-1 gene expression through ERK-induced AML1 phosphorylation Blood, April 15, 2006; 107(8): 3106 - 3113. [Abstract] [Full Text] [PDF] R. Garzon, F. Pichiorri, T. Palumbo, R. Iuliano, A. Cimmino, R. Aqeilan, S. Volinia, D. Bhatt, H. Alder, G. Marcucci, et al. MicroRNA fingerprints during human megakaryocytopoiesis PNAS, March 28, 2006; 103(13): 5078 - 5083. [Abstract] [Full Text] [PDF] Y. Choi, K. E. Elagib, L. L. Delehanty, and A. N. Goldfarb Erythroid Inhibition by the Leukemic Fusion AML1-ETO Is Associated with Impaired Acetylation of the Major Erythroid Transcription Factor GATA-1. Cancer Res., March 15, 2006; 66(6): 2990 - 2996. [Abstract] [Full Text] [PDF] T. Oki, J. Kitaura, K. Eto, Y. Lu, M. Maeda-Yamamoto, N. Inagaki, H. Nagai, Y. Yamanishi, H. Nakajina, H. Kumagai, et al. Integrin {alpha}IIb{beta}3 Induces the Adhesion and Activation of Mast Cells through Interaction with Fibrinogen J. Immunol., January 1, 2006; 176(1): 52 - 60. [Abstract] [Full Text] [PDF] L. F. Peterson, A. Boyapati, V. Ranganathan, A. Iwama, D. G. Tenen, S. Tsai, and D.-E. Zhang The Hematopoietic Transcription Factor AML1 (RUNX1) Is Negatively Regulated by the Cell Cycle Protein Cyclin D3 Mol. Cell. Biol., December 1, 2005; 25(23): 10205 - 10219. [Abstract] [Full Text] [PDF] C. Kuhl, A. Atzberger, F. Iborra, B. Nieswandt, C. Porcher, and P. Vyas GATA1-Mediated Megakaryocyte Differentiation and Growth Control Can Be Uncoupled and Mapped to Different Domains in GATA1 Mol. Cell. Biol., October 1, 2005; 25(19): 8592 - 8606. [Abstract] [Full Text] [PDF] L. Rainis, T. Toki, J. E. Pimanda, E. Rosenthal, K. Machol, S. Strehl, B. Gottgens, E. Ito, and S. Izraeli The Proto-Oncogene ERG in Megakaryoblastic Leukemias Cancer Res., September 1, 2005; 65(17): 7596 - 7602. [Abstract] [Full Text] [PDF] J. D. Growney, H. Shigematsu, Z. Li, B. H. Lee, J. Adelsperger, R. Rowan, D. P. Curley, J. L. Kutok, K. Akashi, I. R. Williams, et al. Loss of Runx1 perturbs adult hematopoiesis and is associated with a myeloproliferative phenotype Blood, July 15, 2005; 106(2): 494 - 504. [Abstract] [Full Text] [PDF] A. K. Rao Decreased platelet Mpl receptor in AML1 haplodeficiency: another piece of the puzzle Blood, June 15, 2005; 105(12): 4545 - 4545. [Full Text] [PDF] P. G. Heller, A. C. Glembotsky, M. J. Gandhi, C. L. Cummings, C. J. Pirola, R. F. Marta, L. I. Kornblihtt, J. G. Drachman, and F. C. Molinas Low Mpl receptor expression in a pedigree with familial platelet disorder with predisposition to acute myelogenous leukemia and a novel AML1 mutation Blood, June 15, 2005; 105(12): 4664 - 4670. [Abstract] [Full Text] [PDF] W. Sun and J. R. Downing Haploinsufficiency of AML1 results in a decrease in the number of LTR-HSCs while simultaneously inducing an increase in more mature progenitors Blood, December 1, 2004; 104(12): 3565 - 3572. [Abstract] [Full Text] [PDF] E. Tenedini, M. E. Fagioli, N. Vianelli, P. L. Tazzari, F. Ricci, E. Tagliafico, P. Ricci, L. Gugliotta, G. Martinelli, S. Tura, et al. Gene expression profiling of normal and malignant CD34-derived megakaryocytic cells Blood, November 15, 2004; 104(10): 3126 - 3135. [Abstract] [Full Text] [PDF] S. Addya, M. A. Keller, K. Delgrosso, C. M. Ponte, R. Vadigepalli, G. E. Gonye, and S. Surrey Erythroid-induced commitment of K562 cells results in clusters of differentially expressed genes enriched for specific transcription regulatory elements Physiol Genomics, September 16, 2004; 19(1): 117 - 130. [Abstract] [Full Text] [PDF] K. E. Elagib, M. Xiao, I. M. Hussaini, L. L. Delehanty, L. A. Palmer, F. K. Racke, M. J. Birrer, G. Shanmugasundaram, M. A. McDevitt, and A. N. Goldfarb Jun Blockade of Erythropoiesis: Role for Repression of GATA-1 by HERP2 Mol. Cell. Biol., September 1, 2004; 24(17): 7779 - 7794. [Abstract] [Full Text] [PDF] H. Liu, M. Holm, X.-Q. Xie, M. Wolf-Watz, and T. Grundstrom AML1/Runx1 Recruits Calcineurin to Regulate Granulocyte Macrophage Colony-stimulating Factor by Ets1 Activation J. Biol. Chem., July 9, 2004; 279(28): 29398 - 29408. [Abstract] [Full Text] [PDF] T. Minami, T. Murakami, K. Horiuchi, M. Miura, T. Noguchi, J.-i. Miyazaki, T. Hamakubo, W. C. Aird, and T. Kodama Interaction between Hex and GATA Transcription Factors in Vascular Endothelial Cells Inhibits flk-1/KDR-mediated Vascular Endothelial Growth Factor Signaling J. Biol. Chem., May 14, 2004; 279(20): 20626 - 20635. [Abstract] [Full Text] [PDF] R. B. Lorsbach, J. Moore, S. O. Ang, W. Sun, N. Lenny, and J. R. Downing Role of RUNX1 in adult hematopoiesis: analysis of RUNX1-IRES-GFP knock-in mice reveals differential lineage expression Blood, April 1, 2004; 103(7): 2522 - 2529. [Abstract] [Full Text] [PDF] T. E. North, T. Stacy, C. J. Matheny, N. A. Speck, and M. F.T.R. de Bruijn Runx1 Is Expressed in Adult Mouse Hematopoietic Stem Cells and Differentiating Myeloid and Lymphoid Cells, But Not in Maturing Erythroid Cells Stem Cells, March 1, 2004; 22(2): 158 - 168. [Abstract] [Full Text] [PDF] L. Sun, G. Mao, and A. K. Rao Association of CBFA2 mutation with decreased platelet PKC-{theta} and impaired receptor-mediated activation of GPIIb-IIIa and pleckstrin phosphorylation: proteins regulated by CBFA2 play a role in GPIIb-IIIa activation Blood, February 1, 2004; 103(3): 948 - 954. [Abstract] [Full Text] [PDF] N. Fossett, K. Hyman, K. Gajewski, S. H. Orkin, and R. A. Schulz Combinatorial interactions of Serpent, Lozenge, and U-shaped regulate crystal cell lineage commitment during Drosophila hematopoiesis PNAS, September 30, 2003; 100(20): 11451 - 11456. [Abstract] [Full Text] [PDF] H. Benchabane and J. L. Wrana GATA- and Smad1-Dependent Enhancers in the Smad7 Gene Differentially Interpret Bone Morphogenetic Protein Concentrations Mol. Cell. Biol., September 15, 2003; 23(18): 6646 - 6661. [Abstract] [Full Text] [PDF]

	Blood Online is supported in part by Genentech BioOncology and Biogen Idec
	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020