Epigenetic effects of chromatin remodeling agents on organotypic cultures

Silvia M. Sirchia, Alice Faversani, Davide Rovina, Maria V. Russo, Leda Paganini, Federica Savi, Claudia Augello, Lorenzo Rosso, Alessandro Del Gobbo, Silvia Tabano, Silvano Bosari, Monica Miozzo

Research output: Contribution to journalArticle

Abstract

Background: Tumor epigenetic defects are of increasing relevance to clinical practice, because they are 'druggable' targets for cancer therapy using chromatin-remodeling agents (CRAs). New evidences highlight the importance of the microenvironment on the epigenome regulation and the need to use culture models able to preserve tissue morphology, to better understand the action of CRAs. Methods & methods: We studied the epigenetic response induced by culturing and CRAs in a preclinical model, preserving ex vivo the original tissue microenvironment and morphology, assessing different epigenetic signatures. Our overall findings suggest that culturing and CRAs cause heterogeneous effects on the genes methylation; CRAs affect the global DNA methylation and can trigger an active DNA demethylation; the culture induces alterations in the histone deacetylase expression. Conclusion: Despite the limited number of cases, these findings can be considered a proof of concept of the possibility to test CRAs epigenetic effects on ex vivo tissues maintained in their native tissue architecture.

Original languageEnglish
Pages (from-to)341-358
Number of pages18
JournalEpigenomics
Volume8
Issue number3
DOIs
Publication statusPublished - Mar 1 2016

Keywords

  • chromatin remodeling agents
  • DNA hydroxymethylation
  • DNA methylation
  • epigenetics
  • HDAC
  • organotypic culture

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

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  • Cite this

    Sirchia, S. M., Faversani, A., Rovina, D., Russo, M. V., Paganini, L., Savi, F., Augello, C., Rosso, L., Del Gobbo, A., Tabano, S., Bosari, S., & Miozzo, M. (2016). Epigenetic effects of chromatin remodeling agents on organotypic cultures. Epigenomics, 8(3), 341-358. https://doi.org/10.2217/epi.15.111