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Genome wide H3K9ac and SAGA occupancy at OX growth phase and RC quiescent phase of yeast metabolic cycle

ABSTRACT: We found acetyl-CoA levels increase when cells are committed to growth. We also found 3 components of the SAGA complex, Spt7p, Sgf73p and Ada3p as well as histones are dynamically acetylated in tune with the acetyl-CoA levels. ChIP-seq study reveals SAGA and H3K9ac predominantly occupy growth genes at the OX growth phase of the yeast metabolic cycle indicating acetyl-CoA levels may drive growth gene transcription program through acetylation of these proteins.

ORGANISM(S): Saccharomyces cerevisiae

PROVIDER: GSE28734 | GEO | 2011/05/19

SECONDARY ACCESSION(S): PRJNA140547

REPOSITORIES: GEO

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Project description:Cytosolic acetyl-coenzyme A is a precursor for many biotechnologically relevant compounds produced by Saccharomyces cerevisiae. In this yeast, cytosolic acetyl-CoA synthesis and growth strictly depend on expression of either the Acs1 or Acs2 isoenzyme of acetyl-CoA synthetase (ACS). Since hydrolysis of ATP to AMP and pyrophosphate in the ACS reaction constrains maximum yields of acetyl-CoA-derived products, this study explores replacement of ACS by two ATP-independent pathways for acetyl-CoA synthesis. After evaluating expression of different bacterial genes encoding acetylating acetaldehyde dehydrogenase (A-ALD) and pyruvate-formate lyase (PFL), acs1M-NM-^T acs2M-NM-^T S. cerevisiae strains were constructed in which A-ALD or PFL successfully replaced ACS. In A-ALD-dependent strains, aerobic growth rates of up to 0.27 h-1 were observed, while anaerobic growth rates of PFL-dependent S. cerevisiae (0.21 h-1) were stoichiometrically coupled to formate production. In glucose-limited chemostat cultures, intracellular metabolite analysis did not reveal major differences between A-ALD-dependent and reference strains. However, biomass yields on glucose of A-ALD- and PFL-dependent strains were lower than those of the reference strain. Transcriptome analysis suggested that reduced biomass yields were caused by acetaldehyde and formate in A-ALD- and PFL-dependent strains, respectively. Transcript profiles also indicated that a previously proposed role of Acs2 in histone acetylation is probably linked to cytosolic acetyl-CoA levels rather than to direct involvement of Acs2 in histone acetylation. While, for the first time, demonstrating that yeast ACS can be fully replaced by alternative reactions, this study demonstrates that further modifications are needed to achieve optimal in vivo efficiencies of the supply of acetyl-CoA as product precursor. To investigate the impact of introduced changes in native pathway of cytosolic acetyl-CoA formation in S. cerevisiae, a DNA microarray-based transcriptome analysis was performed on aerobic or anaerobic, glucose-limited chemostat cultures.

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Genome wide H3K9ac and SAGA occupancy at OX growth phase and RC quiescent phase of yeast metabolic cycle

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