Identification of E2F target genes that are rate limiting for dE2F1-dependent cell proliferation
Article first published online: 17 SEP 2012
Copyright © 2012 Wiley Periodicals, Inc.
Volume 241, Issue 11, pages 1695–1707, November 2012
How to Cite
Herr, A., Longworth, M., Ji, J.-Y., Korenjak, M., MacAlpine, D. M. and Dyson, N. J. (2012), Identification of E2F target genes that are rate limiting for dE2F1-dependent cell proliferation. Dev. Dyn., 241: 1695–1707. doi: 10.1002/dvdy.23857
- Issue published online: 17 OCT 2012
- Article first published online: 17 SEP 2012
- Accepted manuscript online: 12 SEP 2012 02:37PM EST
- Manuscript Accepted: 15 AUG 2012
- NIH. Grant Numbers: HG004279, CA64402, GM53203
Background: Microarray studies have shown that the E2F transcription factor influences the expression of many genes but it is unclear how many of these targets are important for E2F-mediated control of cell proliferation. Results: We assembled a collection of mutant alleles of 44 dE2F1-dependent genes and tested whether these could modify visible phenotypes caused by the tissue-specific depletion of dE2F1. More than half of the mutant alleles dominantly enhanced de2f1-dsRNA phenotypes suggesting that the in vivo functions of dE2F1 can be limited by the reduction in the level of expression of many different targets. Unexpectedly, several mutant alleles suppressed de2f1-dsRNA phenotypes. One of the strongest of these suppressors was Orc5. Depletion of ORC5 increased proliferation in cells with reduced dE2F1 and specifically elevated the expression of dE2F1-regulated genes. Importantly, these effects were independent of dE2F1 protein levels, suggesting that reducing the level of ORC5 did not interfere with the general targeting of dE2F1. Conclusions: We propose that the interaction between ORC5 and dE2F1 may reflect a feedback mechanism between replication initiation proteins and dE2F1 that ensures that proliferating cells maintain a robust level of replication proteins for the next cell cycle. Developmental Dynamics 241:1695–1707, 2012. © 2012 Wiley Periodicals, Inc.