Local enrichment of HP1alpha at telomeres alters their structure and regulation of telomere protection
| Autor: | Bo Huang, Juan Guan, Jen Hsuan Wei, Guido Stadler, Tracy T. Chow, Elizabeth H. Blackburn, Xiaoyu Shi |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Telomerase Chromosomal Proteins Non-Histone Mutant General Physics and Astronomy medicine.disease_cause Histones 0302 clinical medicine Heterochromatin Telomeric Repeat Binding Protein 2 Telomeric Repeat Binding Protein 1 lcsh:Science Chromo shadow domain Cancer Mutation 0303 health sciences Microscopy Multidisciplinary Tumor Telomere Chromatin Cell biology Chromosomal Proteins DNA damage Science Recombinant Fusion Proteins Protein domain Biology General Biochemistry Genetics and Molecular Biology Article Cell Line 03 medical and health sciences Rare Diseases Protein Domains Cell Line Tumor medicine Genetics Humans Epigenetics 030304 developmental biology Lysine General Chemistry Non-Histone Superresolution 030104 developmental biology Chromobox Protein Homolog 5 Cancer cell lcsh:Q 030217 neurology & neurosurgery DNA Damage |
| Zdroj: | Nature communications, vol 9, iss 1 Nature Communications, Vol 9, Iss 1, Pp 1-13 (2018) Nature Communications |
| Popis: | Enhanced telomere maintenance is evident in malignant cancers. While telomeres are thought to be inherently heterochromatic, detailed mechanisms of how epigenetic modifications impact telomere protection and structures are largely unknown in human cancers. Here we develop a molecular tethering approach to experimentally enrich heterochromatin protein HP1α specifically at telomeres. This results in increased deposition of H3K9me3 at cancer cell telomeres. Telomere extension by telomerase is attenuated, and damage-induced foci at telomeres are reduced, indicating augmentation of telomere stability. Super-resolution STORM imaging shows an unexpected increase in irregularity of telomeric structure. Telomere-tethered chromo shadow domain (CSD) mutant I165A of HP1α abrogates both the inhibition of telomere extension and the irregularity of telomeric structure, suggesting the involvement of at least one HP1α-ligand in mediating these effects. This work presents an approach to specifically manipulate the epigenetic status locally at telomeres to uncover insights into molecular mechanisms underlying telomere structural dynamics. Chromatin dynamics is thought to play an important role in the maintenance of telomeres, yet how has remained poorly understood. Here the authors locally enrich heterochromatin protein 1α (HP1α) at human telomeres to provide insights into the crosstalk between epigenetic regulations and structural dynamics at the telomeres. |
| Databáze: | OpenAIRE |
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