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Telomeres reforged with non-telomeric sequences in mouse embryonic stem cellsoa mark
  • Kim, Chuna ;
  • Sung, Sanghyun ;
  • Kim, Jong Seo ;
  • Lee, Hyunji ;
  • Jung, Yoonseok ;
  • Shin, Sanghee ;
  • Kim, Eunkyeong ;
  • Seo, Jenny J. ;
  • Kim, Jun ;
  • Kim, Daeun ;
  • Niida, Hiroyuki ;
  • Kim, V. Narry ;
  • Park, Daechan ;
  • Lee, Junho
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dc.contributor.authorKim, Chuna-
dc.contributor.authorSung, Sanghyun-
dc.contributor.authorKim, Jong Seo-
dc.contributor.authorLee, Hyunji-
dc.contributor.authorJung, Yoonseok-
dc.contributor.authorShin, Sanghee-
dc.contributor.authorKim, Eunkyeong-
dc.contributor.authorSeo, Jenny J.-
dc.contributor.authorKim, Jun-
dc.contributor.authorKim, Daeun-
dc.contributor.authorNiida, Hiroyuki-
dc.contributor.authorKim, V. Narry-
dc.contributor.authorPark, Daechan-
dc.contributor.authorLee, Junho-
dc.date.issued2021-12-01-
dc.identifier.issn2041-1723-
dc.identifier.urihttps://aurora.ajou.ac.kr/handle/2018.oak/31851-
dc.identifier.urihttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85100884760&origin=inward-
dc.description.abstractTelomeres are part of a highly refined system for maintaining the stability of linear chromosomes. Most telomeres rely on simple repetitive sequences and telomerase enzymes to protect chromosomal ends; however, in some species or telomerase-defective situations, an alternative lengthening of telomeres (ALT) mechanism is used. ALT mainly utilises recombination-based replication mechanisms and the constituents of ALT-based telomeres vary depending on models. Here we show that mouse telomeres can exploit non-telomeric, unique sequences in addition to telomeric repeats. We establish that a specific subtelomeric element, the mouse template for ALT (mTALT), is used for repairing telomeric DNA damage as well as for composing portions of telomeres in ALT-dependent mouse embryonic stem cells. Epigenomic and proteomic analyses before and after ALT activation reveal a high level of non-coding mTALT transcripts despite the heterochromatic nature of mTALT-based telomeres. After ALT activation, the increased HMGN1, a non-histone chromosomal protein, contributes to the maintenance of telomere stability by regulating telomeric transcription. These findings provide a molecular basis to study the evolution of new structures in telomeres.-
dc.description.sponsorshipThe authors thank Michael Bustin for sharing HMGN1 antibody. Long read Iso-Seq was provided by the SMRT Grant of MDxK. This work was supported by the National Research Foundation of Korea (NRF-2020R1A2C3003352, NRF-2019R1C1C1008181, and NRF-2020R1C1C101220611) and the Institute for Basic Science (IBS-R008-D1). C.K. was supported by the KRIBB Research Initiative Programme. The authors thank Daisy Sunghee Lim for creating model images 1a, 3d, and 6.-
dc.language.isoeng-
dc.publisherNature Research-
dc.subject.meshAnimals-
dc.subject.meshDNA-Binding Proteins-
dc.subject.meshEpigenomics-
dc.subject.meshHEK293 Cells-
dc.subject.meshHumans-
dc.subject.meshMice-
dc.subject.meshMice, 129 Strain-
dc.subject.meshMice, Inbred C57BL-
dc.subject.meshMouse Embryonic Stem Cells-
dc.subject.meshProteomics-
dc.subject.meshRepetitive Sequences, Nucleic Acid-
dc.subject.meshSequence Analysis, RNA-
dc.subject.meshSingle-Cell Analysis-
dc.subject.meshTelomerase-
dc.subject.meshTelomere-
dc.subject.meshTelomere Homeostasis-
dc.subject.meshTranscription Factors-
dc.titleTelomeres reforged with non-telomeric sequences in mouse embryonic stem cells-
dc.typeArticle-
dc.citation.number1-
dc.citation.titleNature Communications-
dc.citation.volume12-
dc.identifier.bibliographicCitationNature Communications, Vol.12 No.1-
dc.identifier.doi2-s2.0-85100884760-
dc.identifier.pmid33597549-
dc.identifier.scopusid2-s2.0-85100884760-
dc.identifier.urlhttp://www.nature.com/ncomms/index.html-
dc.type.otherArticle-
dc.description.isoatrue-
dc.subject.subareaChemistry (all)-
dc.subject.subareaBiochemistry, Genetics and Molecular Biology (all)-
dc.subject.subareaPhysics and Astronomy (all)-
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