EKLF/KLF1 controls cell cycle entry via direct regulation of E2f2

Tallack, M. R., Keys, J. R., Humbert, P. O. and Perkins, A. C. (2009) EKLF/KLF1 controls cell cycle entry via direct regulation of E2f2. Journal of Biological Chemistry, 284 31: 20966-20974. doi:10.1074/jbc.M109.006346

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads
UQ180291_OA.pdf Full text (open access) application/pdf 2.27MB 0

Author Tallack, M. R.
Keys, J. R.
Humbert, P. O.
Perkins, A. C.
Title EKLF/KLF1 controls cell cycle entry via direct regulation of E2f2
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
Publication date 2009-07-01
Year available 2009
Sub-type Article (original research)
DOI 10.1074/jbc.M109.006346
Open Access Status File (Publisher version)
Volume 284
Issue 31
Start page 20966
End page 20974
Total pages 9
Editor Herbert Tabor
Place of publication Bethesda, MD, U. S. A.
Publisher American Society for Biochemistry & Molecular Biology
Language eng
Subject C1
920101 Blood Disorders
060103 Cell Development, Proliferation and Death
Abstract Differentiation of erythroid cells requires precise control over the cell cycle to regulate the balance between cell proliferation and differentiation. The zinc finger transcription factor, erythroid Krüppel-like factor (EKLF/KLF1), is essential for proper erythroid cell differentiation and regulates many erythroid genes. Here we show that loss of EKLF leads to aberrant entry into S-phase of the cell cycle during both primitive and definitive erythropoiesis. This cell cycle defect was associated with a significant reduction in the expression levels of E2f2 and E2f4, key factors necessary for the induction of S-phase gene expression and erythropoiesis. We found and validated novel intronic enhancers in both the E2f2 and E2f4 genes, which contain conserved CACC, GATA, and E-BOX elements. The E2f2 enhancer was occupied by EKLF in vivo. Furthermore, we were able to partially restore cell cycle dynamics in EKLF−/− fetal liver upon additional genetic depletion of Rb, establishing a genetic causal link between reduced E2f2 and the EKLF cell cycle defect. Finally, we propose direct regulation of the E2f2 enhancer is a generic mechanism by which many KLFs regulate proliferation and differentiation.
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 519718
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
Institute for Molecular Bioscience - Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 42 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 43 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Thu, 03 Sep 2009, 17:45:44 EST by Mr Andrew Martlew on behalf of Institute for Molecular Bioscience