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| Status |
Public on Dec 31, 2015 |
| Title |
Genome-wide mapping of Tet3FL in neural progeniter cells |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
We report that the 5-methylcytosine oxidase Tet3 exists as three isoforms and characterized the full-length isoform containing an N-terminal CXXC domain (Tet3FL). Presence of the CXXC domain reduces Tet3’s enzymatic activity. This CXXC domain binds not only to unmethylated CpGs but its highest affinity is towards 5-carboxylcytosine (5caC). We determined the structure of the CXXC domain - 5caC-DNA complex and showed that disruption of the CXXC-5caC interaction leads to enhanced Tet3 activity. Mapping of genomic binding sites of Tet3FL in neuronal cells shows that Tet3FL is targeted to transcription start sites of genes involved in lysosome function, mRNA processing and key genes of the base excision repair pathway. Our data suggest that the CXXC domain of Tet3FL restricts the protein to a set of unmethylated or 5caC-containing CpG islands and that Tet3FL functions both as a reader of 5caC and as a regulator of 5caC removal by base excision repair.
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| |
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| Overall design |
Examination of genomic binding sites of Tet3FL in neural progeniter cells at day 2 upon neural differentiation and in E15.5 embryonic mouse brain.
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| |
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| Contributor(s) |
Jin S, Wu X, Pfeifer GP |
| Citation(s) |
26774490 |
| Submission date |
Apr 15, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Xiwei Wu |
| E-mail(s) |
xwu@coh.org
|
| Organization name |
City of Hope National Medical Center
|
| Department |
Computational and Quantitative Medicine
|
| Street address |
1500 E. Duarte Rd.
|
| City |
Duarte |
| State/province |
CA |
| ZIP/Postal code |
91010 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
| Samples (10)
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| Relations |
| BioProject |
PRJNA244682 |
| SRA |
SRP041193 |
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