Article

Histone H2B Deacetylation at Lysine 11 Is Required for Yeast Apoptosis Induced by Phosphorylation of H2B at Serine 10

Laboratory of Chromatin Biology, The Rockefeller University, Box 78, New York, New York 10021, USA.
Molecular Cell (Impact Factor: 14.02). 11/2006; 24(2):211-20. DOI: 10.1016/j.molcel.2006.09.008
Source: PubMed

ABSTRACT

Chromatin alterations, induced by covalent histone modifications, mediate a wide range of DNA-templated processes, including apoptosis. Apoptotic chromatin condensation has been causally linked to the phosphorylation of histone H2B (serine 14 in human; serine 10 in yeast, H2BS10ph) in human and yeast cells. Here, we extend these studies by demonstrating a unidirectional, crosstalk pathway between H2BS10 phosphorylation and lysine 11 acetylation (H2BK11ac) in yeast. We demonstrate that the H2BK11 acetyl mark, which exists in growing yeast, is removed upon H(2)O(2) treatment but before H2BS10ph occurs, in a unidirectional fashion. H2B K11Q mutants are resistant to cell death elicited by H(2)O(2), while H2B K11R mutants that mimic deacetylation promote cell death. Our results suggest that Hos3 HDAC deacetylates H2BK11ac, which in turn mediates H2BS10ph by Ste20 kinase. Together, these studies underscore a concerted series of enzyme reactions governing histone modifications that promote a switch from cell proliferation to cell death.

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    • "Emerging evidences suggested that protein post translated modifications often ad jacent or nearby one another within a single protein, leading to regulate protein functi on or important signaling events [66]. For instance, Ahn et al. provided in vivo and in vitro evidence for acetylation and phosphorylation crosstalk between two histone neighboring residues (S10 and K11) in H2B [67], their findings indicated a critical interplay indeed exist between two different histone modifications in close amino acid residues. Acetylation and phosphorylation crosstalk also play an important role in non-histone proteins, for instance, Mittal et al. found that acetylated threonine residue (T179) was located between two phosphor-acceptor serine residues (S176, S180) in the kinase IKKα, and YopJ (a bacterial effector protein) could catalyze the acetylation of IKKα(T179) and block the phosphorylation of critical residues (S176, S180) that was A C C E P T E D M A N U S C R I P T "
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