2026-06-14T10:35:45Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/83172024-11-29T14:27:34Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
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
funder
Ministerio de Economía y Competitividad (España)
funder
Comunidad de Madrid (España)
funder
World Cancer Research Fund International
funder
Botín Foundation
2019-08-28T10:06:46Z
2019-08-28T10:06:46Z
2019-08-20
Elife. 2019 ;8. pii: e44656.
10.7554/eLife.44656
2050-084X
2050-084X
eLife
31426913
http://hdl.handle.net/20.500.12105/8317
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.
eng
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
journal article
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TERRAregulatethetranscriptional_2019.pdf
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TERRAregulatethetranscriptional_figures_2019.pdf
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TERRAregulatethetranscriptional_2019.pdf.txt
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TERRAregulatethetranscriptional_figures_2019.pdf.txt