Yeast Unravels Epigenetic Apoptosis Control: Deadly Chat within a Histone Tail  Didac Carmona-Gutierrez, Frank Madeo  Molecular Cell  Volume 24, Issue 2, Pages 167-169 (October 2006) DOI: 10.1016/j.molcel.2006.10.004 Copyright © 2006 Elsevier Inc. Terms and Conditions

Figure 1 The Basic Molecular Machinery of Yeast Apoptosis Yeast shows a typical apoptotic phenotype including phosphatidylserine externalization, chromatin condensation, and DNA degradation. Accordingly, key players configuring the basic molecular machinery of cell death are conserved in yeast, among others the yeast caspase Yca1, the yeast homolog of mammalian HtrA2/OMI, NMA111, and the apoptosis-inducing factor Aif1. Furthermore, yeast programmed death can also be induced by both replicative and chronological aging and it has been linked to mitochondrial fragmentation, cytochrome c release, and cytoskeletal perturbations. The importance of histone modifications such as acetylation and phosphorylation in the regulation of cell-death execution is becoming evident. For instance, the histone deacetylases Hda1 and Rpd3 and the kinase Ste20 have been demonstrated to play a role in the regulation of yeast apoptosis. Molecular Cell 2006 24, 167-169DOI: (10.1016/j.molcel.2006.10.004) Copyright © 2006 Elsevier Inc. Terms and Conditions

Figure 2 Histone H2B Tail Crosstalk Regulation K11 of the H2B tail is acetylated by Gcn5p. In logarithmically growing yeast cells, this acetylation mark blocks the ability of the Ste20p kinase to phosphorylate its adjacent site, S10. Upon exposure to an apoptotic stimulus, the histone deacetylase Hos3p deacetylates K11 and allows Ste20p to phosphorylate S10, which is required for apoptotic cell death. Hence, the epigenetic shift from acetylation to phosphorylation at two neighboring sites leads to a switch from cell proliferation to cell death. Interestingly, Gcn5p is part of a transcriptional coactivator complex that induces longevity during replicative aging by stimulating expression of stress-response genes that, in turn, are negatively regulated by two HDACs, Rpd3p and Hda1p. Additionally, the kinase Ste20p is a crucial element in the MAPK cascade, which is activated upon pheromone exposure leading to apoptotic cell death. Molecular Cell 2006 24, 167-169DOI: (10.1016/j.molcel.2006.10.004) Copyright © 2006 Elsevier Inc. Terms and Conditions