2026-05-20T22:57:00Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/83172024-11-29T14:27:34Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Marion RM, Rosa María author Montero, Juan J author Lopez de Silanes, Isabel author Graña Castro, Osvaldo author Martinez Rodriguez, Paula author Schoeftner, Stefan author Palacios-Fábrega, José Alejandro author Blasco , MA author 2019-08-20 The mechanisms that regulate pluripotency are still largely unknown. Here, we show that Telomere Repeat Binding Factor 1 (TRF1), a component of the shelterin complex, regulates the genome-wide binding of polycomb and polycomb H3K27me3 repressive marks to pluripotency genes, thereby exerting vast epigenetic changes that contribute to the maintenance of mouse ES cells in a naïve state. We further show that TRF1 mediates these effects by regulating TERRA, the lncRNAs transcribed from telomeres. We find that TERRAs are enriched at polycomb and stem cell genes in pluripotent cells and that TRF1 abrogation results in increased TERRA levels and in higher TERRA binding to those genes, coincidental with the induction of cell-fate programs and the loss of the naïve state. These results are consistent with a model in which TRF1-dependent changes in TERRA levels modulate polycomb recruitment to pluripotency and differentiation genes. These unprecedented findings explain why TRF1 is essential for the induction and maintenance of pluripotency. Elife. 2019 ;8. pii: e44656. 10.7554/eLife.44656 2050-084X 2050-084X eLife 31426913 http://hdl.handle.net/20.500.12105/8317 TERRA TRF1 Chromosomes Gene expression lncRNA Mouse Pluripotency Polycomb Regenerative medicine Stem cells Telomere TERRA regulate the transcriptional landscape of pluripotent cells through TRF1-dependent recruitment of PRC2