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| Status |
Public on Sep 25, 2017 |
| Title |
SETDB1 depletion in primed or naïve ES cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Endogenous retroviruses (ERVs), which are responsible for 10% of spontaneous mouse mutations, are kept under control via several epigenetic mechanisms. The H3K9 histone methyltransferase SETDB1 is essential for ERV repression in embryonic stem cells (ESCs), with DNA methylation also playing an important role. It has been suggested that SETDB1 protects ERVs from TET-dependent DNA demethylation, but the relevance of this mechanism for ERV expression remains unclear. Moreover, previous studies have been performed in primed ESCs, which are not epigenetically or transcriptionally representative of preimplantation embryos. We used naïve ESCs to investigate the role of SETDB1 in ERV regulation and, in particular, its relationship with TET-mediated DNA demethylation. Naïve ESCs show an increased dependency on SETDB1 for ERV silencing when compared to primed ESCs, including at the highly mutagenic intracisternal A particles (IAPs). We found that, in the absence of SETDB1, TET2 activates IAP elements in a catalytic-dependent manner. Surprisingly, however, TET2 does not drive changes in DNA methylation levels at IAPs, suggesting that it regulates these transposons indirectly.
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| Overall design |
SETDB1 was depleted in primed or naïve embryonic stem cells by shRNA, using a non-targeting sequence (shScr) as a control. RNA was extracted to generate rRNA-depleted RNA-seq libraries (3 replicates of each sample).
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| Contributor(s) |
Deniz O, de la Rica L, Cheng K, Spensbeger D, Branco MR |
| Citation missing |
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| |
| Submission date |
Feb 02, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Miguel R Branco |
| E-mail(s) |
m.branco@qmul.ac.uk
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| Organization name |
Blizard Institute
|
| Street address |
4 Newark Street
|
| City |
London |
| ZIP/Postal code |
E1 2AT |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE100864 |
SETDB1 prevents TET2-dependent activation of IAP retroelements in naïve embryonic stem cells |
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| Relations |
| BioProject |
PRJNA369696 |
| SRA |
SRP098765 |
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