|
| Status |
Public on Sep 22, 2014 |
| Title |
Tet proteins in DNA demethylation and cell fate restriction |
| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
Expression profiling by high throughput sequencing
|
| Summary |
DNA methylation at 5-position of cytosine (5mC) is one of the best studied epigenetic modifications that plays important roles in diverse biological processes. Iterative oxidation of 5mC by the Ten-eleven translocation (Tet) family of proteins generates 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC), which can be further processed by DNA repair proteins leading to DNA demethylation. Functional characterization of the Tet proteins has been complicated by the redundancy between the three Tet proteins. Using the CRISPR/Cas9 technology, we have generated mouse embryonic stem cells (ESCs) deficient for all three Tet proteins (TKO). Whole genome bisulphite sequencing (WGBS) analysis revealed that Tet-mediated DNA demethylation mainly occurs distal enhancers as well as promoters that significantly overlap with 5hmC, 5fC and 5caC. Characterization of the Tet TKO ESCs revealed a function for Tet proteins in cell fate restriction as Tet TKO ESCs tend to adopt both primed pluripotent stem cell-like state and 2-cell embryo-like state. In addition, Tet TKO ESCs exhibit elongated telomeres. Thus, our study reveals a role of Tet proteins not only in DNA demethylation, but also in cell fate restriction and telomere maintenance.
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| |
|
| Overall design |
2 samples for WGBS and 2 samples for RNA-seq
|
| |
|
| Contributor(s) |
Lu F, Liu Y, Jiang L, Yamaguchi S, Zhang Y |
| Citation(s) |
25223896 |
| |
| Submission date |
Apr 23, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Lan Jiang |
| E-mail(s) |
lan.jiang@childrens.harvard.edu
|
| Organization name |
Boston Children Hospital
|
| Lab |
Yi Zhang
|
| Street address |
200 Longwood Ave
|
| City |
Boston |
| State/province |
Massachusetts |
| ZIP/Postal code |
02115 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
| Samples (4)
|
|
| Relations |
| BioProject |
PRJNA245171 |
| SRA |
SRP041376 |
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