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DNA methylation profiling to investigate how Tet1 controls maintenance DNA methylation via the regulation of Dppa3 in ESCs

ABSTRACT: DNA methylation profiling to investigate how Tet1 controls maintenance DNA methylation via the regulation of Dppa3 in ESCs

PROVIDER: PRJEB34995 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR3606880.fastq.gz	Fastqsanger.gz
	ERR3606881.fastq.gz	Fastqsanger.gz
	ERR3606882.fastq.gz	Fastqsanger.gz
	ERR3606883.fastq.gz	Fastqsanger.gz
	ERR3606884.fastq.gz	Fastqsanger.gz

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DNA methylation profiling to investigate how Tet1 controls maintenance DNA methylation via the regulation of Dppa3 in ESCs

Project description:DNA methylation profiling using RRBS in wild type and Dppa3 knockout ESCs.

2020-09-30 | E-MTAB-6800 | biostudies-arrayexpress

Tet1 controls maintenance DNA methylation via the regulation of Dppa3

Project description:Tet1 controls maintenance DNA methylation via the regulation of Dppa3

| PRJEB34996 | ENA

TET1 controls maintenance DNA methylation

Project description:TET1 controls maintenance DNA methylation via the regulation of Dppa3

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Tet1 controls maintenance DNA methylation via the regulation of Dppa3

Project description:Dissection of catalytic and non-catalytic functions of Tet1. DNA methylation (RRBS) profiling of wild type, Tet1 knockout and catalytic mutants during EpiLC differentiation.

2020-09-30 | E-MTAB-6785 | biostudies-arrayexpress

Amplicon bisulfite sequencing of LINE-1 elements in TET catalytic mutants and DPPA3 KO ESCs rescued by doxycylin induced overexpression

Project description:Tet1, Tet2 and Tet1/Tet2 catalytic mutants as well as DPPA3 KO ESCs harboring a doxycyclin inducible Dppa3 transgene were induced for several days to monitor LINE-1 methylation levels.

2020-10-23 | E-MTAB-9654 | biostudies-arrayexpress

LINE-1 DNA methylation levels in DPPA3 KO overexpressing DPPA3 mutants

Project description:DPPA3 mutants were overexpressed using a doxycycline system to identify regions in DPPA3 necessary for DNA methylation maintenance suppression

2020-10-22 | E-MTAB-9653 | biostudies-arrayexpress

LINE-1 DNA methylation levels in DPPA3 KO overexpressing DPPA3 mutants

Project description:LINE-1 DNA methylation levels in DPPA3 KO overexpressing DPPA3 mutants

| PRJEB40756 | ENA

Dissection of TET1 catalytic and non-catalytic functions reveals DNA demethylation independent gene and ERV regulation

Project description:Surveillance of DNA methylation in mammals is critical for genome stability and epigenetic regulation. The discovery of the ten-eleven translocation (TET) proteins catalyzing the oxidation from 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) revolutionized the understanding of DNA methylation dynamics. Interestingly, in recent years evidence accumulated that TET1 also harbours non-catalytic functions. However, the role and mechanism of TET1 DNA demethylation independent functions still remain poorly understood. Here, we use genome engineering and quantitative multi-omics approaches to dissect the non-catalytic role of TET1. Strikingly, we find that the majority of transcriptional regulation depends on non-catalytic functions of TET1. To gain insights into possible mechanisms by which TET1 regulates transcription independent of DNA demethylation, we asked if the loss of TET1 is accompanied by changes in the histone modificaiton landscape. To this end, we compared the relative abundances of core histone modifications between Tet1 KO, Tet1 CM and WT mESCs using quantitative LC-MS/MS analysis. Surprisingly, we observed a profound global reduction of pH4Kac and H4K20me3 as well as H3K27me3 in Tet1 KO mESC. Vice versa, the monomethylation states of the latter two residues, H3K27me1 and H4K20me1 were significantly increased in Tet1 KO. Similar to the results from the transcriptome data, most of these changes were specific to Tet1 KO cells.

2022-08-11 | PXD028566 | Pride

ChIP-MS of DPPA3/STELLA in mouse embryonic stem cells

Project description:Genome-wide DNA demethylation is a unique feature of mammalian development and naïve pluripotent stem cells. So far, it was unclear how mammals specifically achieve global DNA hypomethylation, given the high conservation of the DNA (de-)methylation machinery among vertebrates. We found that DNA demethylation requires TET activity but mostly occurs at sites where TET proteins are not bound suggesting a rather indirect mechanism. Among the few specific genes bound and activated by TET proteins was the naïve pluripotency and germline marker Dppa3 (Pgc7, Stella), which undergoes TDG dependent demethylation. The requirement of TET proteins for genome-wide DNA demethylation could be bypassed by ectopic expression of Dppa3. We show that DPPA3 binds and displaces UHRF1 from chromatin and thereby prevents the recruitment and activation of the maintenance DNA methyltransferase DNMT1. We demonstrate that DPPA3 alone can drive global DNA demethylation when transferred to amphibians (Xenopus) and fish (medaka), both species that naturally do not have a Dppa3 gene and exhibit no post-fertilization DNA demethylation. Our results show that TET proteins are responsible for active and - indirectly also for - passive DNA demethylation; while TET proteins initiate local and gene-specific demethylation in vertebrates, the recent emergence of DPPA3 introduced a unique means of genome-wide passive demethylation in mammals and contributed to the evolution of epigenetic regulation during early mammalian development.

2020-10-12 | PXD019794 | Pride

TET1-mediated DNA hydroxy-methylation regulates adult remyelination

Project description:Adult myelination is essential for brain function and response to injury, but the molecular mechanisms remain elusive. Here we identify DNA hydroxy-methylation, an epigenetic mark catalyzed by Ten-Eleven translocation (TET) enzymes, as necessary for adult myelin repair. While DNA hydroxy-methylation and high levels of TET1 were detected in young adult mice during myelin regeneration after demyelination, this process was defective in old mice. Constitutive or inducible lineage-specific ablation of Tet1 (but not of Tet2) recapitulated the age-related decline of DNA hydroxy-methylation and inefficient remyelination. Genome-wide hydroxy-methylation and transcriptomic analysis identified solute carrier gene families as TET1 targets. Lower transcripts for these genes in Tet1 mutants and old mice were associated with swelling at the neuroglial interface, a phenotype detected also in zebrafish Slc12a2b mutants. We conclude that TET1-mediated DNA hydroxy-methylation is necessary for adult myelination after injury, by modulating the levels of the solute carrier SLC12A2 at the axo-myelin interface.

2020-03-14 | GSE137611 | GEO

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