Atypical E2F activity restrains APC/CCCS52A2 function obligatory for endocycle onset.
The endocycle represents an alternative cell cycle that is activated in various developmental processes, including placental formation, Drosophila oogenesis, and leaf development. In endocycling cells, mitotic cell cycle exit is followed by successive doublings of the DNA content, resulting in polyploidy. The timing of endocycle onset is crucial for correct development, because polyploidization is linked with cessation of cell division and initiation of terminal differentiation. The anaphase-promoting complex/cyclosome (APC/C) activator genes CDH1, FZR, and CCS52 are known to promote endocycle onset in human, Drosophila, and Medicago species cells, respectively; however, the genetic pathways governing development-dependent APC/C(CDH1/FZR/CCS52) activity remain unknown. We report that the atypical E2F transcription factor E2Fe/DEL1 controls the expression of the CDH1/FZR orthologous CCS52A2 gene from Arabidopsis thaliana. E2Fe/DEL1 misregulation resulted in untimely CCS52A2 transcription, affecting the timing of endocycle onset. Correspondingly, ectopic CCS52A2 expression drove cells into the endocycle prematurely. Dynamic simulation illustrated that E2Fe/DEL1 accounted for the onset of the endocycle by regulating the temporal expression of CCS52A2 during the cell cycle in a development-dependent manner. Analogously, the atypical mammalian E2F7 protein was associated with the promoter of the APC/C-activating CDH1 gene, indicating that the transcriptional control of APC/C activator genes by atypical E2Fs might be evolutionarily conserved.
Lammens
Tim
T
Department of Plant Systems Biology, Flanders Institute for Biotechnology and Department of Molecular Genetics, Ghent University, 9052 Gent, Belgium.
Boudolf
Véronique
V
Kheibarshekan
Leila
L
Zalmas
L Panagiotis
LP
Gaamouche
Tarik
T
Maes
Sara
S
Vanstraelen
Marleen
M
Kondorosi
Eva
E
La Thangue
Nicholas B
NB
Govaerts
Willy
W
Inzé
Dirk
D
De Veylder
Lieven
L
D064173:Anaphase-Promoting Complex-Cyclosome; D017360:Arabidopsis / Q000166:cytology* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D002453:Cell Cycle; D019143:Evolution, Molecular; D018506:Gene Expression Regulation, Plant; D005966:Glucuronidase / Q000378:metabolism; D008938:Mitosis; D018515:Plant Leaves / Q000254:growth & development; D030821:Plants, Genetically Modified; D011401:Promoter Regions, Genetic; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D043743:Ubiquitin-Protein Ligase Complexes / Q000235:genetics / Q000378:metabolism*
C500416:DEL1 protein, Arabidopsis; D014157:Transcription Factors; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D005966:Glucuronidase
Plant Physiol. 2005 Jun;138(2):734-43
15863702
Plant Cell. 2005 Jun;17(6):1723-36
15863515
Plant Cell. 2005 Jun;17(6):1704-22
15749764
Plant Cell. 2004 Feb;16(2):422-34
14742878
Mol Cell Biol. 2000 Oct;20(20):7613-23
11003657
Cell. 1997 Aug 22;90(4):671-81
9288747
Plant Cell. 2006 Nov;18(11):3145-57
17098811
Cell. 2001 Jun 1;105(5):645-55
11389834
EMBO J. 1999 Aug 16;18(16):4476-84
10449413
Genes Dev. 2001 Dec 15;15(24):3278-85
11751633
Plant Physiol. 2001 Jul;126(3):1214-23
11457971
Oncogene. 2005 Apr 18;24(17):2765-75
15838513
Development. 2008 Apr;135(8):1451-61
18321983
Nature. 1999 Oct 21;401(6755):815-8
10548110
Cell Cycle. 2005 Aug;4(8):1084-92
15970679
Dev Cell. 2008 Jan;14(1):62-75
18194653
Plant J. 1998 Dec;16(6):735-43
10069079
Oncogene. 2005 Apr 18;24(17):2810-26
15838517
Nature. 1976 Jun 17;261(5561):614-5
934306
Curr Biol. 2004 Apr 6;14(7):630-6
15062106
Plant Physiol. 2007 May;144(1):105-20
17351056
Plant Cell. 2003 Jan;15(1):79-92
12509523
Nat Cell Biol. 2007 Feb;9(2):225-32
17187060
Nature. 2006 Jul 27;442(7101):471-4
16810178
Annu Rev Genet. 2006;40:77-105
17094738
Plant Cell. 2003 Dec;15(12):2763-77
14615597
Plant Cell. 2004 Oct;16(10):2683-92
15377755
Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):6410-5
11983922
Dev Biol. 1999 Nov 15;215(2):407-19
10545247
Plant Cell. 2004 Sep;16(9):2350-63
15308755
Curr Biol. 2005 Jan 11;15(1):59-63
15649366
J Biol Chem. 2005 May 6;280(18):18211-20
15722552
Nat Rev Mol Cell Biol. 2006 Sep;7(9):644-56
16896351
Trends Plant Sci. 2002 May;7(5):193-5
11992820
EMBO J. 2002 Mar 15;21(6):1360-8
11889041
EMBO Rep. 2008 Mar;9(3):252-9
18202719
J Biol Chem. 2001 Sep 28;276(39):36354-60
11477067
J Biol Chem. 2003 Oct 24;278(43):42041-9
12893818
Cell. 2001 May 4;105(3):297-306
11348589
Plant J. 2002 Apr;30(2):203-12
12000456