학술논문
Structural basis of telomeric nucleosome recognition by shelterin factor TRF1.
Document Type
Academic Journal
Author
Hu H; MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, UK.; van Roon AM; MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, UK.; Ghanim GE; MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, UK.; Ahsan B; MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, UK.; Oluwole AO; Department of Chemistry, University of Oxford, Oxford, OX1 3QZ UK.; Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford, OX1 3QU UK.; Peak-Chew SY; MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, UK.; Robinson CV; Department of Chemistry, University of Oxford, Oxford, OX1 3QZ UK.; Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford, OX1 3QU UK.; Nguyen THD; MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, UK.
Source
Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101653440 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2375-2548 (Electronic) Linking ISSN: 23752548 NLM ISO Abbreviation: Sci Adv Subsets: MEDLINE
Subject
Language
English
Abstract
Shelterin and nucleosomes are the key players that organize mammalian chromosome ends into the protective telomere caps. However, how they interact with each other at telomeres remains unknown. We report cryo-electron microscopy structures of a human telomeric nucleosome both unbound and bound to the shelterin factor TRF1. Our structures reveal that TRF1 binds unwrapped nucleosomal DNA ends by engaging both the nucleosomal DNA and the histone octamer. Unexpectedly, TRF1 binding shifts the register of the nucleosomal DNA by 1 bp. We discovered that phosphorylation of the TRF1 C terminus and a noncanomical DNA binding surface on TRF1 are critical for its association with telomeric nucleosomes. These insights into shelterin-chromatin interactions have crucial implications for understanding telomeric chromatin organization and other roles of shelterin at telomeres including replication and transcription.