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| Status |
Public on Jun 04, 2024 |
| Title |
CXXC5 stabilizes DNA methylation patterns in mouse embryonic stem cells [Bisulfite-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
Mammalian genomes encode a family of 12 proteins that contain a CXXC zinc finger domain. These domains are known to bind to unmethylated DNA sequences rich in CpG dinucleotides. Most members of this family are large multi-domain proteins that function in the control of DNA methylation and histone methylation patterns. CXXC5 is a smaller member of the family, along with its closest homologue CXXC4. These two proteins lack known catalytic domains. Here we have characterized CXXC5 in mouse embryonic stem (ES) cells. We show that CXXC5 is a nuclear protein that interacts with 5-methylcytosine oxidases (TET proteins). Removal of CXXC5 from ES cells leads to very few changes in gene expression. CXXC5 extensively colocalizes with TET1 and TET2 at CpG islands. CXXC5 inactivation leads to a substantial reduction of DNA methylation levels that affects all genomic compartments including genic and intergenic regions and CpG island shores. No hypermethylation of CpG islands was observed. We propose a model in which CXXC5 serves as an anchor for TET proteins at CpG islands. In the absence of CXXC5, the 5-methylcytosine oxidases become dislodged from CpG islands and are enabled to induce genome-scale DNA demethylation. Thus, CXXC5 serves as a stabilizer of DNA methylation patterns.
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| Overall design |
To gain insight into a role of CXXC5 in mouse embryonic stem cells, we performed whole genome bisulfite sequencing (WGBS) on two wildtype mES smaples and two CXXC5-CXXC4 double knockout mES cell clones.
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| Contributor(s) |
Jin S, Pfeifer GP |
| Citation missing |
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| |
| Submission date |
Jun 03, 2024 |
| Last update date |
Jun 05, 2024 |
| Contact name |
Gerd P. Pfeifer |
| Organization name |
Van Andel Research Institute
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| Department |
Center for Epigenetics
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| Lab |
Pfeifer, Gerd
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| Street address |
333 Bostwick Ave. NE.
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| City |
Grand Rapids |
| State/province |
Michigan |
| ZIP/Postal code |
49503 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA1119400 |
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