Epigenetic gatekeeping enables genome-scale horizontal gene transfer in eukaryotic cells.

Mammalian cells can retain chromosome-scale algal DNA after phagocytic uptake, maintaining more than 16 Mb as telomere-linked structures for 95 generations without selection.

• Why it matters: Eukaryote-to-eukaryote horizontal gene transfer is exceptionally rare, and direct genome-scale evidence for stable foreign genome accommodation in eukaryotic cells has been lacking.
• What they did: Mammalian cells were exposed to intact algal cells via phagocytic uptake, and live-cell imaging plus genome sequencing and cytogenetic analyses tracked early nuclear DNA transfer and long-term retention.
• The result: Retained algal DNA progressively gained DNA methylation and repressive histone marks forming heterochromatin that associated with host chromosomes, and de novo DNA methyltransferase deficiency reduced stable establishment and retention.

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