Fig. 2: Mechanisms for enhanced expression of oncogenes on ecDNA.
From: Modern biology of extrachromosomal DNA: A decade-long voyage of discovery
a Oncogene amplification through ecDNA produces more copies of oncogene, resulting in more transcripts than non-amplified chromosomal loci. b ecDNA chromatin is more accessible, with less repressive histone marks (H3K9me3 and H3K27me3) and repressive DNA methylation, and more active histone marks (H3K4me1/3 and H3K27ac) compared to non-amplified chromosomal loci. c ecDNA formation enables oncogene to hijack distal, non-canonical enhancers, either from the same topologically associated domain (TAD, left), a different TAD (middle), or a different chromosome (right). d ecDNA has profound interactions with chromosomes and other ecDNA molecules. ecDNA-borne nascent long non-coding RNA (lncRNA) coordinates enhancer–gene interactions between ecDNA–chromosome and ecDNA–ecDNA interactions. In addition, BRD4 proteins mediate ecDNA hub formation.
