ABSTRACTExtrachromosomal-circular DNA (eccDNA) are circular-DNA elements that are implicated in cellular processes such as genomic diversification and instability, along with other genomic mechanisms. However, their structure and chromatinization state is poorly understood. Here we identified a 358-bp circular micro-eccDNA molecule derived from the human Titin gene, which was selected for this study based on its size and sequence characteristics, and used atomistic molecular dynamics simulations to study its interaction with nucleosomes and corresponding topological state. We show the presence or absence of bound nucleosomes provides a topological switch between intact and denatured DNA.