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A single change at telomeres controls the ability of cells to generate a complete organism

Pluripotent cells can give rise to all cells of the body, a power that researchers are eager to control because it opens the door to regenerative medicine and organ culture for transplants. But pluripotency is still a black box for science, controlled by unknown genetic (expression of genes) and epigenetic signals (biochemical marks that control gene expression like on/off switches). The Telomeres and Telomerase Group, led by Maria Blasco at the Spanish National Cancer Research Centre (CNIO), now uncovers one of those epigenetic signals, after a detective quest that started almost a decade ago.

It is a piece of the puzzle that explains the observed powerful connection between the phenomenon of pluripotency and telomeres—protective structures at the ends of chromosomes—a kind of butterfly effect in which a protein that is only present in telomeres shows a global action on the genome. This butterfly effect is essential to initiate and maintain pluripotency.

The DNA of telomeres directs the production of long RNA molecules called TERRAs. What the CNIO researchers found is that TERRAs act on key genes for pluripotency through the Polycomb proteins, which control the programs that determine the fate of cells in the early embryo by depositing a biochemical mark on the genes. The on/off switch that regulates TERRAs, in turn, is a protein that is only present in telomeres; this protein is TRF1, one of the components of the telomere-protecting complex called shelterin. The new result is published this week in the journal eLife.

Rosa María Marión et al. TERRA regulate the transcriptional landscape of pluripotent cells through TRF1-dependent recruitment of PRC2, eLife (2019). DOI: 10.7554/eLife.44656

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