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| Status |
Public on Jun 07, 2021 |
| Title |
CTCF is a Barrier for Totipotent-like Reprogramming [Cut&Run] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Totipotent cells have the ability of generating embryonic and extra-embryonic tissues. Interestingly, a rare population of cells with totipotent-like potential was identified within ESC cultures. These cells, known as 2 cell (2C)-like cells, arise from ESC and display similar features to those found in the totipotent 2 cell embryo. However, the molecular determinants of 2C like conversion have not been completely elucidated. Here, we show that CTCF is a barrier for 2C-like reprogramming. Indeed, forced conversion to a 2C-like state by DUX expression was associated with DNA damage at a subset of CTCF binding sites. Endogenous or DUX-induced 2C-like ESC showed decreased CTCF enrichment at known binding sites, suggesting that acquisition of a totipotent-like state is associated with a highly dynamic chromatin architecture. Accordingly, depletion of CTCF in ESC efficiently promoted spontaneous and asynchronous conversion to a totipotent-like state. This phenotypic reprogramming was reversible upon restoration of CTCF levels. Furthermore, we showed that transcriptional activation of the ZSCAN4 cluster was necessary for successful 2C-like reprogramming. In summary, we revealed the intimate relation between CTCF and totipotent-like reprogramming.
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| Overall design |
Cut&Run experiments of CTCF in untreated and DUX-overexpressing ESC lines for 16h or 24h. Cut&Run experiments of CTCF in a population of sorted spontaneously converted ESC into totipotent-like cells expressing LTR-sequences
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| Contributor(s) |
Tillo D, Ruiz S, Olbrich T |
| Citation(s) |
34381034 |
| |
| Submission date |
Jan 20, 2021 |
| Last update date |
Sep 07, 2021 |
| Contact name |
Desiree Tillo |
| E-mail(s) |
desiree.tillo@nih.gov
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| Phone |
+1-240-760-7289
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| Organization name |
NIH/NCI
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| Street address |
41 Center Dr, Room D310
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| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
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| Samples (18)
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| This SubSeries is part of SuperSeries: |
| GSE165162 |
CTCF is a Barrier for Totipotent-like Reprogramming |
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| Relations |
| BioProject |
PRJNA693448 |
| SRA |
SRP302519 |
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