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Blood, 1 August 2006, Vol. 108, No. 3, pp. 886-895. Prepublished online as a Blood First Edition Paper on April 4, 2006; DOI 10.1182/blood-2005-09-008656. This Article Full Text Full Text (PDF) Supplemental Table and Figure All Versions of this Article: blood-2005-09-008656v1 108/3/886    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 Kinross, K. M. Articles by Humbert, P. O. Search for Related Content PubMed PubMed Citation Articles by Kinross, K. M. Articles by Humbert, P. O. Related Collections Hematopoiesis and Stem Cells Red Cells Cell Cycle Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS E2f4 regulates fetal erythropoiesis through the promotion of cellular proliferation Kathryn M. Kinross, Allison J. Clark, Rosa M. Iazzolino, and Patrick Orson Humbert From the Cell Cycle and Cancer Genetics Laboratory, Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Australia; the Department of Pathology and the Department of Biochemistry and Molecular Biology, The University of Melbourne, Melbourne, Australia. The E2F proteins are major regulators of the transcriptional program required to coordinate cell cycle progression and exit. In particular, E2f4 has been proposed to be the principal family member responsible for the regulation of cell cycle exit chiefly through its transcriptional repressive properties. We have previously shown that E2f4–/– mice display a marked macrocytic anemia implicating E2f4 in the regulation of erythropoiesis. However, these studies could not distinguish whether E2f4 was required for differentiation, survival, or proliferation control. Here, we describe a novel function for E2f4 in the promotion of erythroid proliferation. We show that loss of E2f4 results in an impaired expansion of the fetal erythroid compartment in vivo that is associated with impaired cell cycle progression and decreased erythroid proliferation. Consistent with these observations, cDNA microarray analysis reveals cell cycle control genes as one of the major class of genes down-regulated in E2f4–/– FLs, and we provide evidence that E2f4 may directly regulate the transcriptional expression of a number of these genes. We conclude that the macrocytic anemia of E2f4–/– mice results primarily from impaired cellular proliferation and that the major role of E2f4 in fetal erythropoiesis is to promote cell cycle progression and cellular proliferation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. R. Tallack, J. R. Keys, P. O. Humbert, and A. C. Perkins EKLF/KLF1 Controls Cell Cycle Entry via Direct Regulation of E2f2 J. Biol. Chem., July 31, 2009; 284(31): 20966 - 20974. [Abstract] [Full Text] [PDF] S. Noy-Lotan, O. Dgany, R. Lahmi, N. Marcoux, T. Krasnov, N. Yissachar, D. Ginsberg, B. Motro, P. Resnitzky, I. Yaniv, et al. Codanin-1, the protein encoded by the gene mutated in congenital dyserythropoietic anemia type I (CDAN1), is cell cycle-regulated Haematologica, May 1, 2009; 94(5): 629 - 637. [Abstract] [Full Text] [PDF] A. M. Pilon, M. O. Arcasoy, H. K. Dressman, S. E. Vayda, Y. D. Maksimova, J. I. Sangerman, P. 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Menon, W. Kapelle, O. Bogacheva, O. Bogachev, E. Houde, S. Browne, P. Sathyanarayana, and D. M. Wojchowski EPO modulation of cell-cycle regulatory genes, and cell division, in primary bone marrow erythroblasts Blood, October 1, 2007; 110(7): 2361 - 2370. [Abstract] [Full Text] [PDF] V. A. Ruzhynsky, K. A. McClellan, J. L. Vanderluit, Y. Jeong, M. Furimsky, D. S. Park, D. J. Epstein, V. A. Wallace, and R. S. Slack Cell Cycle Regulator E2F4 Is Essential for the Development of the Ventral Telencephalon J. Neurosci., May 30, 2007; 27(22): 5926 - 5935. [Abstract] [Full Text] [PDF]

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