Gcn5 and Rpd3 have a limited role in the regulation of cell cycle transcripts during the G1 and S phases in Saccharomyces cerevisiae.

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.

DNA replication checkpoint promotes G1-S transcription by inactivating the MBF repressor Nrm1.

The cell cycle transcriptional program imposes order on events of the cell-cycle and is a target for signals that regulate cell-cycle progression, including checkpoints required to maintain genome integrity. Neither the mechanism nor functional significance of checkpoint regulation of the cell-cycle transcription program are established. We show that Nrm1, an MBF-specific transcriptional repressor acting at the transition from G(1) to S phase of the cell cycle, is at the nexus between the cell cycle transcriptional program and the DNA replication checkpoint in fission yeast. Phosphorylation of Nrm1 by the Cds1 (Chk2) checkpoint protein kinase, which is activated in response to DNA replication stress, promotes its dissociation from the MBF transcription factor. This leads to the expression of genes encoding components that function in DNA replication and repair pathways important for cell survival in response to arrested DNA replication.