Site specificity analysis of Piccolo NuA4-mediated acetylation for different histone complexes

Yin Ming Kuo, Ryan A. Henry, Song Tan, Jacques Côté, Andrew J. Andrews

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

We have a limited understanding of the site specificity of multisubunit lysine acetyltransferase (KAT) complexes for histonebased substrates, especially in regards to the different complexes formed during nucleosome assembly. Histone complexes could be a major factor in determining the acetylation specificity of KATs. In the present study, we utilized a label-free quantitative MS-based method to determine the site specificity of acetylation catalysed by Piccolo NuA4 on (H3/H4)2 tetramer, tetramer bound DNA(tetrasome) and nucleosome core particle (NCP).Our results show that Piccolo NuA4 can acetylate multiple lysine residues on these three histone complexes, of which NCP is the most favourable, (H3/H4)2 tetramer is the second and tetrasome is the least favourable substrate for Piccolo NuA4 acetylation. Although Piccolo NuA4 preferentially acetylates histone H4 (H4K12), the site specificity of the enzyme is altered with different histone complex substrates. Our results show that before nucleosome assembly is complete, H3K14 specificity is almost equal to that of H4K12 and DNA-histone interactions suppress the acetylation ability of Piccolo NuA4. These data suggest that the H2A/H2B dimer could play a critical role in the increase in acetylation specificity of Piccolo NuA4 for NCP. This demonstrates that histone complex formation can alter the acetylation preference of Piccolo NuA4. Such findings provide valuable insight into regulating Piccolo NuA4 specificity by modulating chromatin dynamics and in turn manipulating gene expression.

Original languageEnglish (US)
Pages (from-to)239-248
Number of pages10
JournalBiochemical Journal
Volume472
Issue number2
DOIs
StatePublished - Dec 1 2015

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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