Chromatin, consisting of DNA, proteins, and RNA, is essential for eukaryotic genome organization and gene regulation, influencing gene expression through its accessibility. Not only that its the accessibility profile holds essential information on the cell type and state, but abnormal chromatin accessibility is also linked to genetic diseases like cancer and Alzheimer’s. Traditional chromatin accessibility methods are next-generation sequencing (NGS) based and struggle with detecting repetitive and large-scale genomic variations. Optical Genome Mapping (OGM) provides high-resolution structural variation (SV) and copy number variation (CNV) detection. We introduce Dam Assisted Fluorescent tagging of Chromatin Accessibility (DAFCA) for OGM, validated in the GM12878 cell line. DAFCA combines chromatin accessibility profiling with SV and CNV detection, offering comprehensive insights into chromatin dynamics and genetic variation. This method has potential clinical applications by offering comprehensive insights into chromatin dynamics and genetic variation.