Extensive and systematic rewiring of histone post-translational modifications in cancer model systems
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Histone post-translational modifications (PTMs) generate a complex combinatorial code that regulates gene expression and nuclear functions, and whose deregulation has been documented in different types of cancers. Therefore, the availability of relevant culture models that can be manipulated and that retain the epigenetic features of the tissue of origin is absolutely crucial for studying the epigenetic mechanisms underlying cancer and testing epigenetic drugs. In this study, we took advantage of quantitative mass spectrometry to comprehensively profile histone PTMs in patient tumor tissues, primary cultures and cell lines from three representative tumor models, breast cancer, glioblastoma and ovarian cancer, revealing an extensive and systematic rewiring of histone marks in cell culture conditions, which includes a decrease of H3K27me2/me3, H3K79me1/me2 and H3K9ac/K14ac, and an increase of H3K36me1/me2. While some changes occur in short-term primary cultures, most of them are instead time-dependent and appear only in long-term cultures. Remarkably, such changes mostly revert in cell line- and primary cell-derived in vivo xenograft models. Taken together, these results support the use of xenografts as the most representative models of in vivo epigenetic processes, suggesting caution when using cultured cells, in particular cell lines and long-term primary cultures, for epigenetic investigations.
Date Issued
2018-05-04
Date Acceptance
2018-03-16
Citation
Nucleic Acids Research, 2018, 46 (8), pp.3817-3832
ISSN
0305-1048
Publisher
Oxford University Press
Start Page
3817
End Page
3832
Journal / Book Title
Nucleic Acids Research
Volume
46
Issue
8
Copyright Statement
© The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License
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licenses
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by-nc
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), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work
is properly cited. For commercial re-use, please contact journals.permissions@oup.com
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License
(http:
//
creativecommons.org
/
licenses
/
by-nc
/
4.0
/
), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work
is properly cited. For commercial re-use, please contact journals.permissions@oup.com
Sponsor
Cancer Research UK
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/29618087
PII: 4956179
Grant Number
C46704/A23110
Subjects
05 Environmental Sciences
06 Biological Sciences
08 Information And Computing Sciences
Developmental Biology
Publication Status
Published
Coverage Spatial
England
Date Publish Online
2018-03-29