title: 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.
authors: Chromatin Biology Laboratory, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. tajbakhshj@cshs.org
authors: Jian
authors: J
authors: Tajbakhsh
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002843:Chromatin / Q000187:drug effects / Q000378:metabolism*; D003596:Cytosine / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects / Q000502:physiology*; D003952:Diagnostic Imaging / Q000379:methods; D055808:Drug Discovery / Q000379:methods*; D004358:Drug Therapy / Q000379:methods*; D044127:Epigenesis, Genetic / Q000502:physiology*; D006801:Humans; D009152:Mutagenicity Tests / Q000379:methods*
chemical_list: D015415:Biomarkers; D002843:Chromatin; D003596:Cytosine