Nucleosome-regulated topological switching in extrachromosomal circular DNAs

Abstract

Extrachromosomal circular DNA are genetic elements that are implicated in cellular processes such as genomic diversification and instability, along with other genomic mechanisms. However, their structure and chromatinization state are poorly understood. Here we identify a 358 base-pair circular microDNA molecule derived from the human Titin gene and use atomistic molecular dynamics simulations to study its interaction with nucleosomes and its corresponding topological state. Our simulations suggest that the presence or absence of bound nucleosomes provides a topological switch between intact and denatured DNA. These results provide insights into the potential biological roles of microDNAs, including their capacity for promoter-less transcription, gene silencing via small RNAs, or the production of micro-peptides.