title: Atypical E2F activity restrains APC/CCCS52A2 function obligatory for endocycle onset.
abstract: 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.
authors.affiliation: Department of Plant Systems Biology, Flanders Institute for Biotechnology and Department of Molecular Genetics, Ghent University, 9052 Gent, Belgium.
authors.forename: Tim
authors.initials: T
authors.lastname: Lammens
authors.forename: Véronique
authors.initials: V
authors.lastname: Boudolf
authors.forename: Leila
authors.initials: L
authors.lastname: Kheibarshekan
authors.forename: L Panagiotis
authors.initials: LP
authors.lastname: Zalmas
authors.forename: Tarik
authors.initials: T
authors.lastname: Gaamouche
authors.forename: Sara
authors.initials: S
authors.lastname: Maes
authors.forename: Marleen
authors.initials: M
authors.lastname: Vanstraelen
authors.forename: Eva
authors.initials: E
authors.lastname: Kondorosi
authors.forename: Nicholas B
authors.initials: NB
authors.lastname: La Thangue
authors.forename: Willy
authors.initials: W
authors.lastname: Govaerts
authors.forename: Dirk
authors.initials: D
authors.lastname: Inzé
authors.forename: Lieven
authors.initials: L
authors.lastname: De Veylder
mesh_terms: 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*
chemical_list: C500416:DEL1 protein, Arabidopsis; D014157:Transcription Factors; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D005966:Glucuronidase
references.citation: Plant Physiol. 2005 Jun;138(2):734-43
references.pmid: 15863702
references.citation: Plant Cell. 2005 Jun;17(6):1723-36
references.pmid: 15863515
references.citation: Plant Cell. 2005 Jun;17(6):1704-22
references.pmid: 15749764
references.citation: Plant Cell. 2004 Feb;16(2):422-34
references.pmid: 14742878
references.citation: Mol Cell Biol. 2000 Oct;20(20):7613-23
references.pmid: 11003657
references.citation: Cell. 1997 Aug 22;90(4):671-81
references.pmid: 9288747
references.citation: Plant Cell. 2006 Nov;18(11):3145-57
references.pmid: 17098811
references.citation: Cell. 2001 Jun 1;105(5):645-55
references.pmid: 11389834
references.citation: EMBO J. 1999 Aug 16;18(16):4476-84
references.pmid: 10449413
references.citation: Genes Dev. 2001 Dec 15;15(24):3278-85
references.pmid: 11751633
references.citation: Plant Physiol. 2001 Jul;126(3):1214-23
references.pmid: 11457971
references.citation: Oncogene. 2005 Apr 18;24(17):2765-75
references.pmid: 15838513
references.citation: Development. 2008 Apr;135(8):1451-61
references.pmid: 18321983
references.citation: Nature. 1999 Oct 21;401(6755):815-8
references.pmid: 10548110
references.citation: Cell Cycle. 2005 Aug;4(8):1084-92
references.pmid: 15970679
references.citation: Dev Cell. 2008 Jan;14(1):62-75
references.pmid: 18194653
references.citation: Plant J. 1998 Dec;16(6):735-43
references.pmid: 10069079
references.citation: Oncogene. 2005 Apr 18;24(17):2810-26
references.pmid: 15838517
references.citation: Nature. 1976 Jun 17;261(5561):614-5
references.pmid: 934306
references.citation: Curr Biol. 2004 Apr 6;14(7):630-6
references.pmid: 15062106
references.citation: Plant Physiol. 2007 May;144(1):105-20
references.pmid: 17351056
references.citation: Plant Cell. 2003 Jan;15(1):79-92
references.pmid: 12509523
references.citation: Nat Cell Biol. 2007 Feb;9(2):225-32
references.pmid: 17187060
references.citation: Nature. 2006 Jul 27;442(7101):471-4
references.pmid: 16810178
references.citation: Annu Rev Genet. 2006;40:77-105
references.pmid: 17094738
references.citation: Plant Cell. 2003 Dec;15(12):2763-77
references.pmid: 14615597
references.citation: Plant Cell. 2004 Oct;16(10):2683-92
references.pmid: 15377755
references.citation: Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):6410-5
references.pmid: 11983922
references.citation: Dev Biol. 1999 Nov 15;215(2):407-19
references.pmid: 10545247
references.citation: Plant Cell. 2004 Sep;16(9):2350-63
references.pmid: 15308755
references.citation: Curr Biol. 2005 Jan 11;15(1):59-63
references.pmid: 15649366
references.citation: J Biol Chem. 2005 May 6;280(18):18211-20
references.pmid: 15722552
references.citation: Nat Rev Mol Cell Biol. 2006 Sep;7(9):644-56
references.pmid: 16896351
references.citation: Trends Plant Sci. 2002 May;7(5):193-5
references.pmid: 11992820
references.citation: EMBO J. 2002 Mar 15;21(6):1360-8
references.pmid: 11889041
references.citation: EMBO Rep. 2008 Mar;9(3):252-9
references.pmid: 18202719
references.citation: J Biol Chem. 2001 Sep 28;276(39):36354-60
references.pmid: 11477067
references.citation: J Biol Chem. 2003 Oct 24;278(43):42041-9
references.pmid: 12893818
references.citation: Cell. 2001 May 4;105(3):297-306
references.pmid: 11348589
references.citation: Plant J. 2002 Apr;30(2):203-12
references.pmid: 12000456