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Nat Struct Mol Biol. 2012 Aug;19(8):819-23. doi: 10.1038/nsmb.2310. Epub 2012 Jul 15.

Phosphorylation of histone H3 Ser10 establishes a hierarchy for subsequent intramolecular modification events.

Author information

1
Department of NMR-supported Structural Biology, Leibniz Institute of Molecular Pharmacology (FMP Berlin), Berlin, Germany.

Abstract

Phosphorylation of Ser10 of histone H3 regulates chromosome condensation and transcriptional activity. Using time-resolved, high-resolution NMR spectroscopy, we demonstrate that histone H3 Ser10 phosphorylation inhibits checkpoint kinase 1 (Chk1)- and protein kinase C (PKC)-mediated modification of Thr11 and Thr6, the respective primary substrate sites of these kinases. On unmodified H3, both enzymes also target Ser10 and thereby establish autoinhibitory feedback states on individual H3 tails. Whereas phosphorylated Ser10 does not affect acetylation of Lys14 by Gcn5, phosphorylated Thr11 impedes acetylation. Our observations reveal mechanistic hierarchies of H3 phosphorylation and acetylation events and provide a framework for intramolecular modification cross-talk within the N terminus of histone H3.

PMID:
22796964
DOI:
10.1038/nsmb.2310
[Indexed for MEDLINE]

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