A competitive transcription factor binding mechanism determines the timing of late cell cycle-dependent gene expression.
Transcriptional control is exerted by the antagonistic activities of activator and repressor proteins. In Saccharomyces cerevisiae, transcription factor complexes containing the MADS box protein Mcm1p are key regulators of cell cycle-dependent transcription at both the G2/M and M/G1 transitions. The homeodomain repressor protein Yox1p acts in a complex with Mcm1p to control the timing of gene expression. Here, we show that Yox1p interacts with Mcm1p through a motif located N terminally to its homeodomain. Yox1p functions as a transcriptional repressor by competing with the forkhead transcription activator protein Fkh2p for binding to Mcm1p through protein-protein interactions at promoters of a subset of Mcm1p-regulated genes. Importantly, this competition is not through binding the same DNA site that is commonly observed. Thus, this study describes a different mechanism for determining the timing of cell cycle-dependent gene expression that involves competition between short peptide motifs in repressor and activator proteins for interaction with a common binding partner.
Darieva
Zoulfia
Z
Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M139PT, UK.
Clancy
Anne
A
Bulmer
Richard
R
Williams
Emma
E
Pic-Taylor
Aline
A
Morgan
Brian A
BA
Sharrocks
Andrew D
AD
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D026341:Minichromosome Maintenance 1 Protein; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D018797:Cell Cycle Proteins; C464958:Fkh2 protein, S cerevisiae; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; C498030:MCM1 protein, S cerevisiae; D026341:Minichromosome Maintenance 1 Protein; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C080459:Yox1 protein, S cerevisiae
Biochim Biophys Acta. 2007 Jan;1775(1):92-102
17014965
Nature. 2001 Jan 25;409(6819):533-8
11206552
Nucleic Acids Res. 2003 May 1;31(9):2279-88
12711672
Biochem Soc Trans. 2006 Nov;34(Pt 5):722-6
17052182
Mol Cell Biol. 1997 Nov;17(11):6653-62
9343429
EMBO J. 2001 Jun 15;20(12):3018-28
11406578
Mol Cell Biol. 1995 Nov;15(11):5917-28
7565744
Nature. 2000 Jul 6;406(6791):94-8
10894549
Nature. 1998 Feb 12;391(6668):660-6
9490409
Dev Cell. 2005 Aug;9(2):261-70
16054032
Curr Biol. 2000 Aug 24;10(16):R586-8
10985373
Eur J Biochem. 2004 Jul;271(14):2855-62
15233782
Mol Cell Biol. 1996 Nov;16(11):6372-84
8887666
Science. 2002 Oct 25;298(5594):799-804
12399584
Curr Biol. 2000 Jul 27-Aug 10;10(15):896-906
10959837
Cell. 2001 Sep 21;106(6):697-708
11572776
Mol Cell Biol. 1994 May;14(5):3283-91
8164681
EMBO J. 2000 Jul 17;19(14):3750-61
10899128
Nature. 2003 Oct 23;425(6960):859-64
14574415
Mol Cell Biol. 2002 Jan;22(2):430-41
11756540
EMBO J. 2007 Oct 17;26(20):4324-34
17898805
Science. 1992 Aug 21;257(5073):1089-95
1509260
Mol Cell Biol. 2004 Nov;24(22):10036-46
15509804
Genes Dev. 1991 May;5(5):751-63
1851120
Curr Biol. 2003 Sep 30;13(19):1740-5
14521842
Nature. 2000 Jul 6;406(6791):90-4
10894548
Mol Cell Biol. 1999 May;19(5):3312-27
10207056
Genes Dev. 2001 Sep 15;15(18):2445-56
11562353
Genes Dev. 2002 Dec 1;16(23):3034-45
12464633
Mol Cell Biol. 1996 May;16(5):2135-43
8628280
Mol Cell Biol. 2007 Dec;27(23):8364-73
17908798
Nature. 2006 Nov 23;444(7118):494-8
17122856
Genes Dev. 2002 Dec 1;16(23):3017-33
12464632
Nucleic Acids Res. 2007;35(15):5203-12
17670796
Genes Dev. 2003 Jul 15;17(14):1789-802
12865300
Mol Cell Biol. 2006 Jun;26(11):4134-48
16705166
Oncogene. 2005 Apr 18;24(17):2746-55
15838511