DNA methylation topology: potential of a chromatin landmark for epigenetic drug toxicology

• Published in: Epigenomics Vol. 3; no. 6; pp. 761 - 770
• Main Author: Tajbakhsh, Jian
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.12.2011
• Subjects: Algorithms; Biomarkers - metabolism; Chromatin; Chromatin - drug effects; Chromatin - metabolism; Cytosine - metabolism; Diagnostic Imaging - methods; DNA Methylation - drug effects; DNA Methylation - physiology; Drug Discovery - methods; Drug Therapy - methods; Epigenesis, Genetic - physiology; Epigenetic inheritance; Genetic toxicology; Humans; Methods; Methylation; Mutagenicity Tests - methods; Properties; United States
• ISSN: 1750-1911; 1750-192X
• DOI: 10.2217/epi.11.101

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.