We have a limited understanding of the site specificity of multi-subunit lysine acetyltransferase (KAT) complexes for histone-based 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.
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Research Article|
November 13 2015
Site specificity analysis of Piccolo NuA4-mediated acetylation for different histone complexes
Yin-Ming Kuo;
Yin-Ming Kuo
*Department of Cancer Biology, Fox Chase Cancer Center, Philadelphia, PA 19111, U.S.A.
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Ryan A. Henry;
Ryan A. Henry
*Department of Cancer Biology, Fox Chase Cancer Center, Philadelphia, PA 19111, U.S.A.
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Song Tan;
Song Tan
†Center for Eukaryotic Gene Regulation, Department of Biochemistry & Molecular Biology, The Pennsylvania State University, University Park, PA 16802, U.S.A.
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Jacques Côté;
Jacques Côté
‡St-Patrick Research Group in Basic Oncology, Laval University Cancer Research Center, CHU de Québec Research Center-Oncology Axis, Quebec City, Quebec, Canada G1R 2J6
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Andrew J. Andrews
Andrew J. Andrews
1
*Department of Cancer Biology, Fox Chase Cancer Center, Philadelphia, PA 19111, U.S.A.
1To whom correspondence should be addressed (email Andrew.Andrews@fccc.edu).
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Publisher: Portland Press Ltd
Received:
June 10 2015
Revision Received:
September 23 2015
Accepted:
September 29 2015
Accepted Manuscript online:
September 29 2015
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2015 Authors; published by Portland Press Limited
2015
Biochem J (2015) 472 (2): 239–248.
Article history
Received:
June 10 2015
Revision Received:
September 23 2015
Accepted:
September 29 2015
Accepted Manuscript online:
September 29 2015
Citation
Yin-Ming Kuo, Ryan A. Henry, Song Tan, Jacques Côté, Andrew J. Andrews; Site specificity analysis of Piccolo NuA4-mediated acetylation for different histone complexes. Biochem J 1 December 2015; 472 (2): 239–248. doi: https://doi.org/10.1042/BJ20150654
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