The transcriptional network activated by Cln3 cyclin at the G1-to-S transition of the yeast cell cycle.
BACKGROUND
The G1-to-S transition of the cell cycle in the yeast Saccharomyces cerevisiae involves an extensive transcriptional program driven by transcription factors SBF (Swi4-Swi6) and MBF (Mbp1-Swi6). Activation of these factors ultimately depends on the G1 cyclin Cln3.


RESULTS
To determine the transcriptional targets of Cln3 and their dependence on SBF or MBF, we first have used DNA microarrays to interrogate gene expression upon Cln3 overexpression in synchronized cultures of strains lacking components of SBF and/or MBF. Secondly, we have integrated this expression dataset together with other heterogeneous data sources into a single probabilistic model based on Bayesian statistics. Our analysis has produced more than 200 transcription factor-target assignments, validated by ChIP assays and by functional enrichment. Our predictions show higher internal coherence and predictive power than previous classifications. Our results support a model whereby SBF and MBF may be differentially activated by Cln3.


CONCLUSIONS
Integration of heterogeneous genome-wide datasets is key to building accurate transcriptional networks. By such integration, we provide here a reliable transcriptional network at the G1-to-S transition in the budding yeast cell cycle. Our results suggest that to improve the reliability of predictions we need to feed our models with more informative experimental data.
Ferrezuelo
Francisco
F
Departament de Ciències Mèdiques Bàsiques, Institut de Recerca Biomèdica de Lleida, Universitat de Lleida, Montserrat Roig 2, 25008 Lleida, Spain. ferrezuelof@cmb.udl.cat
Colomina
Neus
N
Futcher
Bruce
B
Aldea
Martí
M
D047369:Chromatin Immunoprecipitation; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D004271:DNA, Fungal / Q000378:metabolism; D030541:Databases, Genetic; D016193:G1 Phase / Q000235:genetics*; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D053263:Gene Regulatory Networks / Q000235:genetics*; D005800:Genes, Fungal / Q000235:genetics; D014644:Genetic Variation; D016013:Likelihood Functions; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D015203:Reproducibility of Results; D016196:S Phase / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
C079895:CLN3 protein, S cerevisiae; D016213:Cyclins; D004271:DNA, Fungal; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors