Differentially Isotope-Labeled Nucleosomes To Study Asymmetric Histone Modification Crosstalk by Time-Resolved NMR Spectroscopy

Stamatios Liokatis, Rebecca Klingberg, Song Tan, Dirk Schwarzer

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Post-translational modifications (PTMs) of histones regulate chromatin structure and function. Because nucleosomes contain two copies each of the four core histones, the establishment of different PTMs on individual “sister” histones in the same nucleosomal context, that is, asymmetric histone PTMs, are difficult to analyze. Here, we generated differentially isotope-labeled nucleosomes to study asymmetric histone modification crosstalk by time-resolved NMR spectroscopy. Specifically, we present mechanistic insights into nucleosomal histone H3 modification reactions in cis and in trans, that is, within individual H3 copies or between them. We validated our approach by using the H3S10phK14ac crosstalk mechanism, which is mediated by the Gcn5 acetyltransferase. Moreover, phosphorylation assays on methylated substrates showed that, under certain conditions, Haspin kinase is able to produce nucleosomes decorated asymmetrically with two distinct types of PTMs.

Original languageEnglish (US)
Pages (from-to)8262-8265
Number of pages4
JournalAngewandte Chemie - International Edition
Volume55
Issue number29
DOIs
StatePublished - Jan 1 2016

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Nucleosomes
Crosstalk
Isotopes
Histones
Nuclear magnetic resonance spectroscopy
Phosphorylation
Assays
Substrates
Acetyltransferases
Chromatin
Phosphotransferases

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)

Cite this

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Differentially Isotope-Labeled Nucleosomes To Study Asymmetric Histone Modification Crosstalk by Time-Resolved NMR Spectroscopy. / Liokatis, Stamatios; Klingberg, Rebecca; Tan, Song; Schwarzer, Dirk.

In: Angewandte Chemie - International Edition, Vol. 55, No. 29, 01.01.2016, p. 8262-8265.

Research output: Contribution to journalArticle

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