DNA Methylation Topology: Potential of a Chromatin Landmark for Epigenetic Drug Toxicology

Abstract

Targeting chromatin and its basic components through epigenetic drug therapy has become an increased focus in the treatment of complex diseases. This boost calls for the implementation of high-throughput cell-based assays that exploit the increasing knowledge about epigenetic mechanisms and their interventions for genotoxicity testing of epigenetic drugs. 3D quantitative DNA methylation imaging is a novel approach for detecting drug-induced DNA demethylation and concurrent heterochromatin decondensation/reorganization in cells through the analysis of differential nuclear distribution patterns of methylcytosine and gDNA visualized by fluorescence and processed by machine-learning algorithms. Utilizing 3D DNA methylation patterns is a powerful precursor to a series of fully automatable assays that employ chromatin structure and higher organization as novel pharmacodynamic biomarkers for various epigenetic drug actions.

KEYWORDS::

• cell-based assay
• DNA methylation imaging
• epigenetic drug
• genotoxicity
• heterochromatin
• nuclear topology

Financial&competing interests disclosure

The Department of Surgery at the Cedars-Sinai Medical Center and the National Institutes of Health are acknowledged for funding epigenetics projects that led to the consideration of the issues discussed in this manuscript. The author is a shareholder of Epilumina Inc. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

The Department of Surgery at the Cedars-Sinai Medical Center and the National Institutes of Health are acknowledged for funding epigenetics projects that led to the consideration of the issues discussed in this manuscript. The author is a shareholder of Epilumina Inc. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.