Histone modifications as regulators of life and death in Saccharomyces cerevisiae

Abstract

Apoptosis or programmed cell death is an integrated, genetically controlled suicide program that not only regulates tissue homeostasis of multicellular organisms, but also the fate of damaged and aged cells of lower eukaryotes, such as the yeast Saccharomyces cerevisiae. Recent years have revealed key apoptosis regulatory proteins in yeast that play similar roles in mammalian cells. Apoptosis is a process largely defined by characteristic structural rearrangements in the dying cell that include chromatin condensation and DNA fragmentation. The mechanism by which chromosomes restructure during apoptosis is still poorly understood, but it is becoming increasingly clear that altered epigenetic histone modifications are fundamental parameters that influence the chromatin state and the nuclear rearrangements within apoptotic cells. The present review will highlight recent work on the epigenetic regulation of programmed cell death in budding yeast.

Keywords: Saccharomyces cerevisiae; apoptosis; autophagy; epigenetics; histone modification; yeast.

Figure 1. FIGURE 1: Specific histone modifications that have been shown to be associated with apoptotic cell death and lifespan regulation in S. cerevisiae.

Modified lysine residues are highlighted in cyan, modified serine residues in red, and modified tyrosine residues in grey. Ac, acetylation; Me, methylation; Ph, phosphorylation; Ub, ubiquitination.

Figure 2. FIGURE 2: Schematic presentation as to how altered histone modifications might promote cell death.

Changes in histone modifications will lead to structural rearrangements in the chromatin, which in turn will affect processes, such as transcription, DNA replication and repair, nucleocytoplasmic localization of proteins. Altered transcription may change the expression of regulatory apoptotic factors, cell cycle, autophagy, ribosomal and other vital genes, which in turn will affect apoptotic signalling, cell cycle progression and/or ribosome biogenesis, which may lead to cell death. Replication stress, genomic and mRNA instability, defects in nucleocytoplasmic transport as well as other vital signalling pathways may also lead to cell death as a consequence of altered histone marks.