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Extensive and systematic rewiring of histone post-translational modifications in cancer model systems

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Title: Extensive and systematic rewiring of histone post-translational modifications in cancer model systems
Authors: Noberini, R
Osti, D
Miccolo, C
Richichi, C
Lupia, M
Corleone, G
Hong, S-P
Colombo, P
Pollo, B
Fornasari, L
Pruneri, G
Magnani, L
Cavallaro, U
Chiocca, S
Minucci, S
Pelicci, G
Bonaldi, T
Item 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.
Issue Date: 4-May-2018
Date of Acceptance: 16-Mar-2018
URI: http://hdl.handle.net/10044/1/58961
DOI: https://dx.doi.org/10.1093/nar/gky224
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 (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/Funder: Cancer Research UK
Funder's Grant Number: C46704/A23110
Keywords: 05 Environmental Sciences
06 Biological Sciences
08 Information And Computing Sciences
Developmental Biology
Publication Status: Published
Conference Place: England
Open Access location: https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gky224/4956179
Online Publication Date: 2018-03-29
Appears in Collections:Division of Surgery
Division of Cancer



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