From the wings to the center stage of chromosomes
| Autor: | Keiji Okamoto, Hiroyuki Seimiya |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
DNA transcription Regulator DNA-binding protein TRF2 Biology extra-telomeric DNA secondary structure Biochemistry Genome genome-wide 03 medical and health sciences chemistry.chemical_compound Gene expression Animals histone mark Telomeric Repeat Binding Protein 2 Editors' Picks Epigenetics Molecular Biology Genetics telomere Binding Sites G-quadruplex epigenetics 030102 biochemistry & molecular biology Chromosome Promoter Cell Biology telomere repeat-binding factor 2 Telomere G-Quadruplexes shelterin complex 030104 developmental biology chemistry gene regulation DNA DNA Damage |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.h119.011587 |
| Popis: | The role of the telomere repeat-binding factor 2 (TRF2) in telomere maintenance is well-established. However, recent findings suggest that TRF2 also functions outside telomeres, but relatively little is known about this function. Herein, using genome-wide ChIP-Seq assays of TRF2-bound chromatin from HT1080 fibrosarcoma cells, we identified thousands of TRF2-binding sites within the extra-telomeric genome. In light of this observation, we asked how TRF2 occupancy is organized within the genome. Interestingly, we found that extra-telomeric TRF2 sites throughout the genome are enriched in potential G-quadruplex–forming DNA sequences. Furthermore, we validated TRF2 occupancy at several promoter G-quadruplex motifs, which did adopt quadruplex forms in solution. TRF2 binding altered expression and the epigenetic state of several target promoters, indicated by histone modifications resulting in transcriptional repression of eight of nine genes investigated here. Furthermore, TRF2 occupancy and target gene expression were also sensitive to the well-known intracellular G-quadruplex–binding ligand 360A. Together, these results reveal an extensive genome-wide association of TRF2 outside telomeres and that it regulates gene expression in a G-quadruplex–dependent fashion. |
| Databáze: | OpenAIRE |
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