Abstract
Activation of cell cycle regulated transcription during the G1-to-S transition initiates S phase entry and cell cycle commitment. The molecular mechanisms involving G1/S transcriptional regulation are well established and have been shown to be evolutionary conserved from yeast to humans. Previous work has suggested that changes to the chromatin state, specifically through histone acetylation, has an important role in the regulation of G1/S transcription in both yeast and human cells. Here we investigate the role of histone acetylation in G1/S transcriptional regulation in the budding yeast Saccharomyces cerevisiae. Our work shows that histone acetylation at specific sites at G1/S target gene promoters peaks at the G1-to-S transition, coinciding with their peak transcription levels. Acetylation at G1/S target promoters is significantly reduced upon deletion of the previously implicated histone acetyltransferase Gcn5, but G1/S cell cycle regulated transcription is largely unaffected. The histone deacetylase Rpd3, suggested to have a role in Whi5-dependent repression, is required for full repression of G1/S target genes in the G1 and S phases. However, in the context of transcriptionally active levels during the G1-to-S transition, this seems to play a minor role in the regulation of cell cycle transcription. Our data suggests that histone acetylation might modulate the amplitude of G1/S cell cycle regulated transcription in Saccharomyces cerevisiae, but has a limited role in its overall regulation.
Highlights
Cell cycle regulated transcription plays an important role in cell cycle control; in most eukaryotic cells there are three main transcriptional waves associated with distinct stages of the cell cycle: G1/S, G2/M and M/G11
We wanted to establish if, in budding yeast, histone acetylation levels at G1/S target promoters change during the cell cycle and how this correlates with G1/S transcript levels
We focused on acetylation of histone H3 Lysine 9 and Lysine 14 (H3K9ac and H3K14ac), known residues acetylated by the histone acetyltransferase (HAT) Gcn[531], previously shown to be recruited to G1/S target promoters[5]
Summary
Cell cycle regulated transcription plays an important role in cell cycle control; in most eukaryotic cells there are three main transcriptional waves associated with distinct stages of the cell cycle: G1/S, G2/M and M/G11. For example the histone acetyltransferase (HAT) Gcn[5] has been linked to the regulation of G1/S transcription and is required for accurate G1-to-S transition[11] SBF is a transcriptional activator whose activity is inhibited by Whi[5] in early G1 phase[21,22], whilst MBF is a transcriptional repressor and acts together with its co-repressor Nrm[1] outside of G1 phase[23] The role of these transcriptional regulators is well established and it has been suggested that histone acetylation plays an important part in how these complexes control G1/S transcription. Gcn[5], the yeast HAT subunit of the transcription co-activator complex SAGA28,29 has been shown to bind both SBF and MBF target genes[5,30]
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