Circular ecDNA promotes accessible chromatin and high oncogene...

Circular ecDNA promotes accessible chromatin and high oncogene expression
Published: 20 November 2019
Abstract
Oncologies are commonly amplified on particles of extrachromosomal DNA (ecDNA) in cancer but our understanding of the structure of ecDNA and its effect on gene regulation is limited. Here, by integrating ultrastructural imaging, long-range optical mapping and computational analysis of whole-genome sequencing, we demonstrate the structure of circular ecDNA. Pan-cancer analyses reveal that oncogenes encoded on ecDNA are among the most highly expressed genes in the transcriptome of the tumours, linking increased copy number with high transcription levels. Quantitative assessment of the chromatin state reveals that although ecDNA is packaged into chromatin with intact domain structure, it lacks higher-order compaction that is typical of chromosomes and displays significantly enhanced chromatin accessibility. Furthermore, ecDNA is shown to have a significantly greater number of ultra-long-range interactions with active chromatin, which provides insight into how the structure of circular ecDNA affects oncogene function, and connects ecDNA biology with modern cancer genomics and epigenetics.
https://www.nature.com/articles/s41586-019-1763-5

Deoxymab 3E10 is an auto antibody that penetrates live cell nuclei by binding to DNA or its fragments outside of cells (ecDNA) and then following it into cell nuclei through a nucleoside transporter. Once in the nucleus Deoxymab 3E10 interferes with DNA repair processes and kills DNA repair deficient cancer cells ...