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Nat Commun. 2018 Apr 18;9(1):1548. doi: 10.1038/s41467-018-03916-3.

TERRA recruitment of polycomb to telomeres is essential for histone trymethylation marks at telomeric heterochromatin.

Author information

1
Telomeres and Telomerase Group, Molecular Oncology Program, Melchor Fernández Almagro 3, E-28029, Madrid, Spain.
2
Confocal Microscopy Unit, Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro 3, E-28029, Madrid, Spain.
3
Cancer Epigenetics Laboratory, Nanomaterials and Nanotechnology Research Center (CINN-CSIC)-Universidad de Oviedo, Institute of Oncology of Asturias (IUOPA) and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Avda De la Vega, 4-6, 33940, El Entrego, Spain.
4
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Drive Aiguader 88, 08003, Barcelona, Spain.
5
Universitat Pompeu Fabra (UPF), 08003, Barcelona, Spain.
6
Telomeres and Telomerase Group, Molecular Oncology Program, Melchor Fernández Almagro 3, E-28029, Madrid, Spain. mblasco@cnio.es.

Abstract

TERRAs are long non-coding RNAs generated from the telomeres. Lack of TERRA knockout models has hampered understanding TERRAs' functions. We recently identified chromosome 20q as one of the main origins of human TERRAs, allowing us to generate the first 20q-TERRA knockout models and to demonstrate that TERRAs are essential for telomere length maintenance and protection. Here, we use ALT 20q-TERRA knockout cells to address a direct role of TERRAs in telomeric heterochromatin formation. We find that 20q-TERRAs are essential for the establishment of H3K9me3, H4K20me3, and H3K27me3 heterochromatin marks at telomeres. At the mechanistic level, we find that TERRAs bind to PRC2, responsible for catalyzing H3K27 tri-methylation, and that its localization to telomeres is TERRA-dependent. We further demonstrate that PRC2-dependent H3K27me3 at telomeres is required for the establishment of H3K9me3, H4K20me3, and HP1 binding at telomeres. Together, these findings demonstrate an important role for TERRAs in telomeric heterochromatin assembly.

PMID:
29670078
PMCID:
PMC5906467
DOI:
10.1038/s41467-018-03916-3
[Indexed for MEDLINE]
Free PMC Article

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