Erythroid Kruppel-Like factor regulates E2F4 and the G1 Cdk inhibitor, p18

Perkins, Andrew C., Keys, Janelle R., Hodge, Denise J. and Tallack, Michael R. (2005). Erythroid Kruppel-Like factor regulates E2F4 and the G1 Cdk inhibitor, p18. In: Abstracts of the American Society of Hematology 47th annual meeting. American Society of Hematology 47th Annual Meeting, Atlanta, Georgia, (393A-393A). 10-13 December 2005.

Author Perkins, Andrew C.
Keys, Janelle R.
Hodge, Denise J.
Tallack, Michael R.
Title of paper Erythroid Kruppel-Like factor regulates E2F4 and the G1 Cdk inhibitor, p18
Conference name American Society of Hematology 47th Annual Meeting
Conference location Atlanta, Georgia
Conference dates 10-13 December 2005
Proceedings title Abstracts of the American Society of Hematology 47th annual meeting   Check publisher's open access policy
Journal name Blood   Check publisher's open access policy
Place of Publication Washington, DC, United States
Publisher American Society of Hematology
Publication Year 2005
Sub-type Poster
Open Access Status Not Open Access
ISSN 0006-4971
Volume 106
Issue 11 Part 1
Start page 393A
End page 393A
Total pages 1
Language eng
Abstract/Summary Erythroid Kruppel-Like Factor (EKLF) is a zinc finger transcription factor which is essential for ß-globin gene expression. Knockout mice die from anemia at E15, but restoration of globin chain imbalance does not rescue anemia or increase survival. Cell lines derived from EKLF null mice undergo proliferation arrest upon reactivation of a conditional EKLF-ER fusion protein, suggesting a role in cell cycle control. A transcriptional profiling experiment comparing the global gene expression in EKLF null and wild type fetal liver identified many differentially expressed genes, a number of which function in G1 and at the G1/S checkpoint of the cell cycle. The Cyclin dependent kinase (Cdk) inhibitor, p18, and the S phase transcription factor E2F4 were both found to be significantly down regulated in EKLF null mice and this result was confirmed by real-time PCR. Interestingly, E2F4 knockout mice have a similar phenotype to EKLF knockout mice. Bioinformatic searches of the p18 and E2F4 genes shows that each contains phylogenetically conserved CACC box motifs capable of binding EKLF within longer regions of conservation in promoter and intron regions. The p18 gene contains two conserved CACCC sites upstream of the start of transcription, which are required for EKLF dependent promoter activity in luciferase reporter assays. The transcription factor E2F4 contains a conserved EKLF-binding CACC site within an intron that is closely associated with two conserved GATA1 binding sites. We show by a chromatin immunoprecipitation (ChIP) assays that the E2F4 intron and p18 promoter are occupied by EKLF in vivo. Together, these results suggest that EKLF is likely to directly regulate expression of key cell cycle genes in vivo to drive the switch from proliferation to differentiation of erythrocytes. The loss of EKLF is likely to result in aberrant proliferation and predisposition to leukemia.
Subjects 1103 Clinical Sciences
1102 Cardiovascular Medicine and Haematology
Q-Index Code EX
Q-Index Status Provisional Code
Institutional Status UQ
Additional Notes Blood (ASH Annual Meeting Abstracts) 2005 106: Abstract 1357

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Created: Fri, 05 Mar 2010, 20:39:36 EST by Laura McTaggart on behalf of Institute for Molecular Bioscience