phorylation of the N-terminal tail of histone H2B was essential for apoptosis-induced chromatin condensation.128,129 Subsequently, serine 14 was identified as the phosphorylated residue in apoptotic mammalian cells.130 The corresponding phosphorylation on S10 of yeast H2B was confirmed to be essential for hydrogen peroxide -induced chromatin condensation and apoptosis.122,131 Phosphorylation of H2B S10 in yeast is mediated by the sterile 20 kinase, while the homologous Mst1 modifies H2BS14 in mammals.130,131 Deletion of Ste20 abrogates H2BS10ph, increases cell survival under H2O2 treatment, as does mutation of serine 10 to non-phosphorylatable alanine. In contrast, mutation of S10 to glutamate, which mimics phosphorylation, promotes cell death and induces constitutive chromatin compaction.132 Thus, H2BS10ph appears to play a key role in apoptotic chromatin condensation. While further investigation is necessary to understand the mechanisms by which this mark can induce such drastic chromatin structure changes, a number of studies have addressed the issue of its regulation. It has been demonstrated that the K11, immediately adjacent to H2BS10, can be acetylated in a Gcn5-dependent manner and is enriched in exponentially growing cells.133 More recently, it was shown that H2BS10 phosphorylation is negatively regulated by the acetylation state of H2BK11, pointing to a mutually exclusive existence of these marks in the tail of H2B.132 Deacetylation of H2BK11 by the Hos3 HDAC is a prerequisite for H2BS10 phosphorylation by Ste20 and for subsequent induction of apoptotic chromatin compaction. In addition to its extensively studied role in DDR, phosphorylation of H2AXS139 in mammals was recently shown www.landesbioscience.com epigenetics 1103 2012 Landes Bioscience. Do not distribute. This table summarizes the histone Luteolin 7-O-β-D-glucoside residues currently known to be phosphorylated in vivo; identified responsible kinases are indicated as well as the cellular processes implicated. Sc, Saccharomyces cerevisiae; Hs, Homo sapiens; Dm, Drosophila melanogaster; , kinase speculated without being formally tested. These coordinates count methionine as the first amino acid, unlike the other histone coordinates. to function in apoptosis.93 Notably, H2AX phosphorylation increases upon DNA fragmentation and apoptosis.134,135 Mst1 has been PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19811088 identified as the kinase responsible for apoptotic H2AX phosphorylation.136 Overexpression of Mst1 induces phosphorylation of H2AXS139 in HeLa cells, accompanied by DNA fragmentation. In line with this, a study by the Pommier group found that H2BS14 phosphorylation coincides with H2AX staining at the nuclear periphery following induction of apoptosis by death receptor agonists such as TRAIL or FasLigand, 
or by treatment with staurosporine.137 Furthermore, it was demonstrated that a defect of H2AXY142 dephosphorylation resulted in recruitment of the pro-apoptotic factor JNK1, rather than the repair apparatus, to H2AX.41 Based on such evidence, Solier et al. proposed the existence of an H2AX-H2B phosphorylation code during apoptosis in mammalian cells. They suggested that the interplay between phosphorylation of H2BS14, H2AXS139 and H2AXY142 determines the cell fate decision between repair and apoptosis, with H2BS14ph being a hallmark of the latter.137 H3T45 phosphorylation was also observed to occur during apoptosis. While this site has been identified as the target of the PKC kinase in vitro and in vivo in normally cycling human cells,138 its