Related Experiment Video
Updated: Mar 24, 2026
Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
Epigenetic effects of chromatin remodeling agents on organotypic cultures
Silvia M Sirchia1, Alice Faversani2, Davide Rovina1
1Medical Genetics, Department of Health Sciences, Università degli Studi di Milano, 20142 Milano, Italy.
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.
Insights
Chromatin-remodeling agents (CRAs) show potential for cancer therapy by targeting epigenetic defects. This study demonstrates ex vivo testing of CRAs on tissue models preserving native architecture, revealing their epigenetic effects.
Area of Science:
- Oncology
- Epigenetics
- Cancer Therapy
Background:
- Tumor epigenetic defects are critical, druggable targets in cancer therapy.
- Chromatin-remodeling agents (CRAs) offer therapeutic potential.
- The tumor microenvironment influences epigenome regulation, necessitating models that preserve tissue morphology for studying CRAs.
Purpose of the Study:
- To investigate the epigenetic response to culturing and CRAs in a preclinical model.
- To assess the effects of CRAs on epigenetic signatures while preserving native tissue architecture ex vivo.
- To understand how culture conditions and CRAs impact gene methylation and histone deacetylase expression.
Main Methods:
- Utilized a preclinical model preserving ex vivo tissue microenvironment and morphology.
- Assessed various epigenetic signatures in response to culturing and CRA treatment.
- Analyzed gene methylation patterns and histone deacetylase expression.
Main Results:
- Culturing and CRAs induced heterogeneous effects on gene methylation.
- CRAs impacted global DNA methylation and could initiate active DNA demethylation.
- Culture conditions led to alterations in histone deacetylase expression.
Conclusions:
- The study provides a proof of concept for testing CRA epigenetic effects on ex vivo tissues.
- Preserving native tissue architecture is crucial for evaluating CRA efficacy.
- Findings support the development of advanced culture models for cancer epigenetics research.
Related Concept Videos
01:32Chromatin Modification in iPS Cells
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
03:17Inheritance of Chromatin Structures
02:54Nucleosome Remodeling
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
01:37Epigenetic Regulation
X-chromosome...
01:46Epigenetic Regulation
02:25Spreading of Chromatin Modifications
Writers
The writer...