TY - JOUR TI - TERRA regulate the transcriptional landscape of pluripotent cells through TRF1-dependent recruitment of PRC2 AU - Marión, Rosa María AU - Montero, Juan J AU - López de Silanes, Isabel AU - Graña-Castro, Osvaldo AU - Martínez, Paula AU - Schoeftner, Stefan AU - Palacios-Fábrega, José Alejandro AU - Blasco, Maria A A2 - Tyler, Jessica K A2 - Lee, Jeannie T A2 - Chu, Hsueh Ping VL - 8 PY - 2019 DA - 2019/08/20 SP - e44656 C1 - eLife 2019;8:e44656 DO - 10.7554/eLife.44656 UR - https://doi.org/10.7554/eLife.44656 AB - 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. KW - TRF1 KW - telomere KW - pluripotency KW - TERRA KW - polycomb KW - lncRNA JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -