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| Status |
Public on Aug 17, 2017 |
| Title |
Massive reshaping of genome - nuclear lamina interactions during oncogene induced senescence (genome tiling) |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by genome tiling array
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| Summary |
Background. Cellular senescence is a mechanism that virtually irreversibly suppresses the proliferative capacity of cells in response to various stress signals. This includes the expression of activated oncogenes, which cause Oncogene-Induced Senescence (OIS). A body of evidence points to the involvement of chromatin reorganization, including the formation of senescence-associated heterochromatic foci (SAHF). The nuclear lamina (NL) is an important contributor to genome organization and has been involved in cellular senescence and organismal aging. It interacts with multiple regions of the genome called lamina-associated domains (LADs). Some LADs are cell type-specific, while others are conserved between cell types and are referred to as constitutive LADs. Here, we used DamID to investigate the changes in genome-NL interactions in a model of OIS triggered by the expression of the BRAFV600E oncogene. Results. We found that OIS cells lose most of their constitutive LADs (cLADS), suggesting the loss of a specific mechanism that targets cLADs to the NL. In addition, multiple genes relocated to the NL. Unexpectedly, they were not repressed, implying the abrogation of the repressive activity of the NL during OIS. Finally, OIS cells displayed an increased association of telomeres with the NL. Conclusions. Our study reveals that senescent cells acquire a new type of LAD organization and suggest the existence of as yet unknown mechanisms that tether cLADs to the NL and repress gene expression at the NL.
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| Overall design |
Examination of gene expression in cycling cells, after oncogene induced senescence, and after quiescence
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| Contributor(s) |
Lenain C, de Graaf CA, Pagie L, van Steensel B, Peeper D |
| Citation(s) |
28916540 |
| Submission date |
Jan 07, 2016 |
| Last update date |
Nov 19, 2017 |
| Contact name |
Carolyn A de Graaf |
| E-mail(s) |
degraaf@wehi.edu.au
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| Organization name |
Walter and Eliza Hall Institute
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| Street address |
1G Royal Parade
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| City |
Parkville |
| ZIP/Postal code |
3052 |
| Country |
Australia |
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| Platforms (1) |
| GPL10559 |
NimbleGen HD2 Human whole genome custom array 2.1M [090310_LP_til_HX1] |
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| Samples (1) |
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| This SubSeries is part of SuperSeries: |
| GSE76605 |
Massive reshaping of genome - nuclear lamina interactions during oncogene induced senescence |
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| Relations |
| BioProject |
PRJNA308323 |
