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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 (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 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 Author home page(s): Patrick Orson Humbert 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 15, 2005 Accepted March 15, 2006 E2f4 regulates fetal erythropoiesis through the promotion of cellular proliferation Kathryn M Kinross, Allison J Clark, Rosa M Iazzolino, and Patrick Orson Humbert* Cell Cycle and Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, Melbourne, Australia * Corresponding author; email: patrick.humbert{at}petermac.org. 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 impaired expansion of the fetal erythroid compartment in vivo which 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 downregulated 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? 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