Work

The landscape and regulatory potential of eccDNAs in mammalian preimplantation embryos

Year: 2026

Type: article

Abstract: Extrachromosomal circular DNA is an emerging regulatory element implicated in genomic stability and gene regulation, yet its role in preimplantation development remains elusive. Here, we report the widespread presence of extrachromosomal circular DNA in preimplantation embryos, characterized by homologous junction sequences and originating from genomic regions enriched for active histone marks and RNA Polymerase II occupancy. Functional perturbations demonstrate that RNA Polymerase II inhibition suppresses extrachromosomal circular DNA production, whereas disruption of the Fanconi anemia pathway elevates it, suggesting that transcription-replication conflicts affect its biogenesis. Notably, extrachromosomal circular DNA levels surge during major zygotic genome activation. Synthetic extrachromosomal circular DNAs carrying putative enhancers for the zygotic genome activation genes Mycn and Egfl7, and the developmental gene Emx1, significantly upregulate the expression of their respective genes upon transfection into fibroblasts and zygotes. Collectively, this study unveils the extrachromosomal circular DNA landscape in preimplantation embryos, elucidates a transcription-replication conflict mechanism underlying its generation, and establishes its regulatory potential during mammalian preimplantation development. Extrachromosomal circular DNA (eccDNA) is a regulatory element involved in genomic stability and gene regulation. This study identifies widespread eccDNA in early mammalian embryos. These eccDNAs arise from active genomic regions, increase during a major wave of gene activation, and can regulate key developmental genes.

Source: Nature Communications

DOI: 10.1038/s41467-026-71227-z