Telomeres reforged with non-telomeric sequences in mouse embryonic stem cells

Chuna Kim, Sanghyun Sung, Jong-Seo Kim, Hyunji Lee, Yoonseok Jung, Sanghee Shin, Eunkyeong Kim, Jenny J. Seo, Jun Kim, Daeun Kim, Hiroyuki Niida, V. Narry Kim, Daechan Park () and Junho Lee ()
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Chuna Kim: Seoul National University
Sanghyun Sung: Seoul National University
Jong-Seo Kim: Seoul National University
Hyunji Lee: Seoul National University
Yoonseok Jung: Institute for Basic Science
Sanghee Shin: Seoul National University
Eunkyeong Kim: Seoul National University
Jenny J. Seo: Seoul National University
Jun Kim: Seoul National University
Daeun Kim: Ajou University
Hiroyuki Niida: Hamamatsu University School of Medicine
V. Narry Kim: Seoul National University
Daechan Park: Ajou University
Junho Lee: Seoul National University

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract Telomeres 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.

Date: 2021
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DOI: 10.1038/s41467-021-21341-x

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