The shelterin component TRF2 mediates columnar stacking of human telomeric chromatin
Telomere repeat binding factor 2 (TRF2) is an essential component of the telomeres and also plays an important role in a number of other non-telomeric processes. Detailed knowledge of the binding and interaction of TRF2 with telomeric nucleosomes is limited. Here, we study the binding of TRF2 to in...
| Main Authors: | , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2024
|
| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/174944 |
| _version_ | 1826128628398686208 |
|---|---|
| author | Wong, Sook Yi Soman, Aghil Korolev, Nikolay Surya, Wahyu Chen, Qinming Shum, Wayne van Noort, John Nordenskiöld, Lars |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Wong, Sook Yi Soman, Aghil Korolev, Nikolay Surya, Wahyu Chen, Qinming Shum, Wayne van Noort, John Nordenskiöld, Lars |
| author_sort | Wong, Sook Yi |
| collection | NTU |
| description | Telomere repeat binding factor 2 (TRF2) is an essential component of the telomeres and also plays an important role in a number of other non-telomeric processes. Detailed knowledge of the binding and interaction of TRF2 with telomeric nucleosomes is limited. Here, we study the binding of TRF2 to in vitro-reconstituted kilobasepair-long human telomeric chromatin fibres using electron microscopy, single-molecule force spectroscopy and analytical ultracentrifugation sedimentation velocity. Our electron microscopy results revealed that full-length and N-terminally truncated TRF2 promote the formation of a columnar structure of the fibres with an average width and compaction larger than that induced by the addition of Mg2+, in agreement with the in vivo observations. Single-molecule force spectroscopy showed that TRF2 increases the mechanical and thermodynamic stability of the telomeric fibres when stretched with magnetic tweezers. This was in contrast to the result for fibres reconstituted on the 'Widom 601' high-affinity nucleosome positioning sequence, where minor effects on fibre stability were observed. Overall, TRF2 binding induces and stabilises columnar fibres, which may play an important role in telomere maintenance. |
| first_indexed | 2024-10-01T07:27:44Z |
| format | Journal Article |
| id | ntu-10356/174944 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T07:27:44Z |
| publishDate | 2024 |
| record_format | dspace |
| spelling | ntu-10356/1749442024-04-22T15:32:44Z The shelterin component TRF2 mediates columnar stacking of human telomeric chromatin Wong, Sook Yi Soman, Aghil Korolev, Nikolay Surya, Wahyu Chen, Qinming Shum, Wayne van Noort, John Nordenskiöld, Lars School of Biological Sciences Medicine, Health and Life Sciences Chromatin structure Electron microscopy Telomere repeat binding factor 2 (TRF2) is an essential component of the telomeres and also plays an important role in a number of other non-telomeric processes. Detailed knowledge of the binding and interaction of TRF2 with telomeric nucleosomes is limited. Here, we study the binding of TRF2 to in vitro-reconstituted kilobasepair-long human telomeric chromatin fibres using electron microscopy, single-molecule force spectroscopy and analytical ultracentrifugation sedimentation velocity. Our electron microscopy results revealed that full-length and N-terminally truncated TRF2 promote the formation of a columnar structure of the fibres with an average width and compaction larger than that induced by the addition of Mg2+, in agreement with the in vivo observations. Single-molecule force spectroscopy showed that TRF2 increases the mechanical and thermodynamic stability of the telomeric fibres when stretched with magnetic tweezers. This was in contrast to the result for fibres reconstituted on the 'Widom 601' high-affinity nucleosome positioning sequence, where minor effects on fibre stability were observed. Overall, TRF2 binding induces and stabilises columnar fibres, which may play an important role in telomere maintenance. Ministry of Education (MOE) Submitted/Accepted version This work has been supported by the Singapore Ministry of Education (MOE) Academic Research Fund (AcRF) Tier 1 (2021-T1-002-0820) and Tier 3(MOE2019-T3-1-012) grants. 2024-04-17T01:13:27Z 2024-04-17T01:13:27Z 2024 Journal Article Wong, S. Y., Soman, A., Korolev, N., Surya, W., Chen, Q., Shum, W., van Noort, J. & Nordenskiöld, L. (2024). The shelterin component TRF2 mediates columnar stacking of human telomeric chromatin. The EMBO Journal, 43(1), 87-111. https://dx.doi.org/10.1038/s44318-023-00002-3 0261-4189 https://hdl.handle.net/10356/174944 10.1038/s44318-023-00002-3 38177309 2-s2.0-85181627965 1 43 87 111 en 2021-T1-002-0820 MOE2019-T3-1-012 The EMBO journal © 2024 The Author(s). All rights reserved. This article may be downloaded for personal use only. Any other use requires prior permission of the copyright holder. The Version of Record is available online at http://doi.org/10.1038/s44318-023-00002-3. application/pdf |
| spellingShingle | Medicine, Health and Life Sciences Chromatin structure Electron microscopy Wong, Sook Yi Soman, Aghil Korolev, Nikolay Surya, Wahyu Chen, Qinming Shum, Wayne van Noort, John Nordenskiöld, Lars The shelterin component TRF2 mediates columnar stacking of human telomeric chromatin |
| title | The shelterin component TRF2 mediates columnar stacking of human telomeric chromatin |
| title_full | The shelterin component TRF2 mediates columnar stacking of human telomeric chromatin |
| title_fullStr | The shelterin component TRF2 mediates columnar stacking of human telomeric chromatin |
| title_full_unstemmed | The shelterin component TRF2 mediates columnar stacking of human telomeric chromatin |
| title_short | The shelterin component TRF2 mediates columnar stacking of human telomeric chromatin |
| title_sort | shelterin component trf2 mediates columnar stacking of human telomeric chromatin |
| topic | Medicine, Health and Life Sciences Chromatin structure Electron microscopy |
| url | https://hdl.handle.net/10356/174944 |
| work_keys_str_mv | AT wongsookyi theshelterincomponenttrf2mediatescolumnarstackingofhumantelomericchromatin AT somanaghil theshelterincomponenttrf2mediatescolumnarstackingofhumantelomericchromatin AT korolevnikolay theshelterincomponenttrf2mediatescolumnarstackingofhumantelomericchromatin AT suryawahyu theshelterincomponenttrf2mediatescolumnarstackingofhumantelomericchromatin AT chenqinming theshelterincomponenttrf2mediatescolumnarstackingofhumantelomericchromatin AT shumwayne theshelterincomponenttrf2mediatescolumnarstackingofhumantelomericchromatin AT vannoortjohn theshelterincomponenttrf2mediatescolumnarstackingofhumantelomericchromatin AT nordenskioldlars theshelterincomponenttrf2mediatescolumnarstackingofhumantelomericchromatin AT wongsookyi shelterincomponenttrf2mediatescolumnarstackingofhumantelomericchromatin AT somanaghil shelterincomponenttrf2mediatescolumnarstackingofhumantelomericchromatin AT korolevnikolay shelterincomponenttrf2mediatescolumnarstackingofhumantelomericchromatin AT suryawahyu shelterincomponenttrf2mediatescolumnarstackingofhumantelomericchromatin AT chenqinming shelterincomponenttrf2mediatescolumnarstackingofhumantelomericchromatin AT shumwayne shelterincomponenttrf2mediatescolumnarstackingofhumantelomericchromatin AT vannoortjohn shelterincomponenttrf2mediatescolumnarstackingofhumantelomericchromatin AT nordenskioldlars shelterincomponenttrf2mediatescolumnarstackingofhumantelomericchromatin |