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Mol Genet Genomics. 2015 Oct;290(5):2031-46. doi: 10.1007/s00438-015-1051-5. Epub 2015 May 10.

Global alterations of the transcriptional landscape during yeast growth and development in the absence of Ume6-dependent chromatin modification.

Author information

1
Inserm U1085-IRSET, University of Rennes 1, 35042, Rennes, France.
2
INRA, UMR 703, ONIRIS, 44307, Nantes, France.
3
Biozentrum, University of Basel, 4056, Basel, Switzerland.
4
INSA, UMR CNRS 5504 and INRA 792, 31077, Toulouse, France.
5
School of Osteopathic Medicine, Rowan University, Stratford, NJ, 08084, USA.
6
Inserm U1085-IRSET, University of Rennes 1, 35042, Rennes, France. michael.primig@inserm.fr.

Abstract

Chromatin modification enzymes are important regulators of gene expression and some are evolutionarily conserved from yeast to human. Saccharomyces cerevisiae is a major model organism for genome-wide studies that aim at the identification of target genes under the control of conserved epigenetic regulators. Ume6 interacts with the upstream repressor site 1 (URS1) and represses transcription by recruiting both the conserved histone deacetylase Rpd3 (through the co-repressor Sin3) and the chromatin-remodeling factor Isw2. Cells lacking Ume6 are defective in growth, stress response, and meiotic development. RNA profiling studies and in vivo protein-DNA binding assays identified mRNAs or transcript isoforms that are directly repressed by Ume6 in mitosis. However, a comprehensive understanding of the transcriptional alterations, which underlie the complex ume6Δ mutant phenotype during fermentation, respiration, or sporulation, is lacking. We report the protein-coding transcriptome of a diploid MAT a/α wild-type and ume6/ume6 mutant strains cultured in rich media with glucose or acetate as a carbon source, or sporulation-inducing medium. We distinguished direct from indirect effects on mRNA levels by combining GeneChip data with URS1 motif predictions and published high-throughput in vivo Ume6-DNA binding data. To gain insight into the molecular interactions between successive waves of Ume6-dependent meiotic genes, we integrated expression data with information on protein networks. Our work identifies novel Ume6 repressed genes during growth and development and reveals a strong effect of the carbon source on the derepression pattern of transcripts in growing and developmentally arrested ume6/ume6 mutant cells. Since yeast is a useful model organism for chromatin-mediated effects on gene expression, our results provide a rich source for further genetic and molecular biological work on the regulation of cell growth and cell differentiation in eukaryotes.

KEYWORDS:

Interactome; Isw2; Rpd3; Sin3; Transcriptome; Ume6

PMID:
25957495
PMCID:
PMC5469029
DOI:
10.1007/s00438-015-1051-5
[Indexed for MEDLINE]
Free PMC Article

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