Transcriptional plasticity through differential assembly of a multiprotein activation complex.
Cell adaptation to the environment often involves induction of complex gene expression programs under the control of specific transcriptional activators. For instance, in response to cadmium, budding yeast induces transcription of the sulfur amino acid biosynthetic genes through the basic-leucine zipper activator Met4, and also launches a program of substitution of abundant glycolytic enzymes by isozymes with a lower content in sulfur. We demonstrate here that transcriptional induction of PDC6, which encodes a pyruvate decarboxylase isoform with low sulfur content, is directly controlled by Met4 and its DNA-binding cofactors the basic-helix-loop-helix protein Cbf1 and the two homologous zinc finger proteins Met31 and Met32. Study of Cbf1 and Met31/32 association with PDC6 allowed us to find a new mechanism of recruitment of Met4, which allows PDC6 being differentially regulated compared to sulfur amino acid biosynthetic genes. Our findings provide a new example of mechanism allowing transcriptional plasticity within a regulatory network thanks to a definite toolbox comprising a unique master activator and several dedicated DNA-binding cofactors. We also show evidence suggesting that integration of PDC6 to the Met4 regulon may have occurred recently in the evolution of the Saccharomyces cerevisiae lineage.
Cormier
Laëtitia
L
CNRS, Centre de Génétique Moléculaire, Gif-sur-Yvette, France.
Barbey
Régine
R
Kuras
Laurent
L
D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism; D050976:Basic-Leucine Zipper Transcription Factors / Q000378:metabolism*; D001665:Binding Sites; D004271:DNA, Fungal / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011767:Pyruvate Decarboxylase / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; C064042:CBF1 protein, S cerevisiae; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; C073675:MET4 protein, S cerevisiae; C106764:Met31 protein, S cerevisiae; C106765:Met32 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D011767:Pyruvate Decarboxylase
EMBO J. 1996 May 15;15(10):2519-29
8665859
Cell Div. 2006 Aug 08;1:16
16895602
PLoS Genet. 2008 Apr 25;4(4):e1000053
18437200
Mol Cell Biol. 1997 Jul;17(7):3640-8
9199298
PLoS Genet. 2009 May;5(5):e1000485
19436716
Mol Cell Biol. 2006 Apr;26(8):3149-63
16581789
Nature. 2004 Apr 8;428(6983):617-24
15004568
Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W369-73
16845028
Mol Cell. 2002 Apr;9(4):713-23
11983164
Science. 2001 Jul 13;293(5528):297-300
11452124
Proc Natl Acad Sci U S A. 1996 May 28;93(11):5208-12
8643554
FEBS Lett. 1995 Jun 19;367(1):15-8
7601277
Genes Dev. 1994 Apr 15;8(8):970-80
7926781
Environ Toxicol Chem. 2001 Oct;20(10):2353-60
11596770
EMBO J. 1992 Nov;11(11):4103-9
1327757
Genetics. 2007 Jun;176(2):877-90
17435223
Nature. 2004 Sep 2;431(7004):99-104
15343339
Microbiol Mol Biol Rev. 1997 Dec;61(4):503-32
9409150
EMBO J. 2005 Feb 9;24(3):521-32
15660125
Cell. 1990 May 4;61(3):437-46
2185892
Mol Cell Biol. 1992 Apr;12(4):1719-27
1549123
EMBO J. 1997 Aug 1;16(15):4689-97
9303313
Yeast. 1998 Jul;14(10):953-61
9717241
Mol Cell Biol. 1990 Jun;10(6):2458-67
2188087
EMBO J. 1998 Nov 2;17(21):6327-36
9799240
Mol Biol Cell. 2005 Apr;16(4):1872-82
15689486
Proc Int Conf Intell Syst Mol Biol. 1994;2:28-36
7584402
Gene. 1996 Nov 7;179(1):171-7
8955644
Genome Biol. 2004;5(12):R95
15575969
J Biol Chem. 2000 Oct 20;275(42):32611-6
10921921
Mol Cell. 2002 Jul;10(1):69-80
12150908
Nature. 1997 Jun 12;387(6634):708-13
9192896
Cell. 1985 Oct;42(3):913-21
2996783
J Biol Chem. 2006 Apr 28;281(17):11744-54
16497670
Appl Environ Microbiol. 2008 Apr;74(8):2259-66
18281432
Cell. 2000 Aug 4;102(3):303-14
10975521
EMBO J. 2000 Jan 17;19(2):282-94
10637232
EMBO J. 2006 Oct 4;25(19):4436-47
16977312
EMBO J. 2000 Apr 3;19(7):1613-24
10747029
EMBO J. 1994 Jan 1;13(1):180-9
8306960
Nature. 1993 May 6;363(6424):38-45
8479534
EMBO J. 1990 Dec;9(12):4017-26
2249662