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

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  • dc.contributor.author Montero, Juan J.
  • dc.contributor.author López-Silanes, Isabel
  • dc.contributor.author Megías, Diego
  • dc.contributor.author Fraga, Mario F.
  • dc.contributor.author Castells García, Àlvaro, 1991-
  • dc.contributor.author Blasco, Maria A.
  • dc.date.accessioned 2019-11-26T07:53:48Z
  • dc.date.available 2019-11-26T07:53:48Z
  • dc.date.issued 2018
  • dc.description.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.
  • dc.description.sponsorship We thank to R. Torres and S. Rodriguez for advice in the CRISPR-Cas9 technology and helpful discussions. We are indebted to Sylvia Gutiérrez Erlandsson, principal investigator of the confocal microscopy Group at the National Centre of Biotechnology, Madrid (Spain), because, without her generous help, we could not have performed the super-resolution microscopy. Research in the Blasco lab is funded by the Spanish Ministry of Economy and Competitiveness Projects (SAF2013-45111-R and SAF2015-72455-EXP), the World Cancer Research (WCR) Project (16-1177), and the Fundación Botín (Spain).
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Montero JJ, López-Silanes I, Megías D, F Fraga M, Castells-García Á, Blasco MA. TERRA recruitment of polycomb to telomeres is essential for histone trymethylation marks at telomeric heterochromatin. Nat Commun. 2018;9(1):1548. DOI: 10.1038/s41467-018-03916-3
  • dc.identifier.doi http://dx.doi.org/10.1038/s41467-018-03916-3
  • dc.identifier.issn 2041-1723
  • dc.identifier.uri http://hdl.handle.net/10230/42974
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.ispartof Nature Communications. 2018;9(1):1548
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2013-45111-R
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2015-72455-EXP
  • dc.rights © The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Telomeres
  • dc.title TERRA recruitment of polycomb to telomeres is essential for histone trymethylation marks at telomeric heterochromatin
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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