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| Status |
Public on Jun 03, 2019 |
| Title |
SIRT7 tethering of L1 elements to the nuclear lamina mediates their transcriptional repression |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Long interspersed elements-1 (LINE-1, L1) are retrotransposons that hold the capacity of selfpropagation in the genome with potential mutagenic outcomes. How somatic cells restrict L1 activity and how this process becomes dysfunctional during aging and in cancer cells is poorly understood. L1s are enriched at lamin associated domains, heterochromatic regions of the nuclear periphery. Whether this association is necessary for their repression has been elusive. Here we show that the sirtuin family member SIRT7 participates in the epigenetic transcriptional repression of L1 genome-wide in both mouse and human cells. SIRT7 depletion leads to increased L1 expression and retrotransposition. Mechanistically, we identify a novel interplay between SIRT7 and Lamin A/C in L1 repression. Our results demonstrate that SIRT7-mediated H3K18 deacetylation regulates L1 expression by promoting L1 association with elements of the nuclear lamina. The failure of such activity might contribute to the observed genome instability and compromised viability in SIRT7 knockout mice. Overall, our results reveal a novel function of SIRT7 on chromatin organization by mediating the anchoring of L1 to the nuclear envelope, and a new mechanism by which the nuclear lamina maintains genome integrity.
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| Overall design |
Chromatin from 14.5 day WT and SirT7-/- MEFs or the human K562 cell line was subjected to ChIP using antibodies raised against SIRT7 and H3K18Ac and subjected to high-throughput sequencing.
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| Contributor(s) |
Thackray JK, Serrano L |
| Citation(s) |
31226208 |
| Submission date |
Nov 15, 2017 |
| Last update date |
Sep 03, 2019 |
| Contact name |
Joshua K Thackray |
| E-mail(s) |
thackray@rutgers.edu
|
| Organization name |
Rutgers University
|
| Department |
Human Genetics Institute of New Jersey
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| Lab |
Jay Tischfield Lab
|
| Street address |
145 Bevier Road
|
| City |
Piscataway |
| State/province |
NEW JERSEY |
| ZIP/Postal code |
08854 |
| Country |
USA |
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| Platforms (2) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA418599 |
| SRA |
SRP125063 |
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