Tet3 KO in lung smooth muscle cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Thomas Boettger
PROVIDER: E-MTAB-10144 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Ten-eleven translocation (Tet) hydroxylases (Tet1-3) oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). In neurons increased 5hmC levels within gene bodies correlate positively with gene expression. The mechanisms controlling Tet activity and 5hmC levels are poorly understood. In particular, it is not known how the neuronal Tet3 isoform lacking a DNA binding domain is targeted to the DNA. To identify factors binding to Tet3 we screened for proteins that co-precipitate with Tet3 from mouse retina and identified the transcriptional repressor Rest as a highly enriched Tet3-specific interactor. Rest was able to enhance Tet3 hydroxylase activity after co-expression and overexpression of Tet3 activated transcription of Rest-target genes. Moreover, we found that Tet3 also interacts with Nsd3 and two other H3K36 methyltransferases and is able to induce H3K36 trimethylation. We propose a mechanism for transcriptional activation in neurons that involves Rest-guided targeting of Tet3 to the DNA for directed 5hmC-generation and Nsd3-mediated H3K36 trimethylation.
2015-04-02 | PXD001857 | Pride
Project description:Tet3 is an Fe2+-dependent enzyme that oxidizes genomic 5-methylcytosine to 5-hydroxymethylcytosine with the help of alpha-ketoglutarate and oxygen. It is the most abundant Tet enzyme in differentiated tissues including brain. Adult brain contains the highest 5-hydroxymethylcytosine levels. How alpha-ketoglutarate is made available for the oxidation of mC in brain cells and how the Tet activity is linked to neural activity are unsolved questions. Our experiments with full mouse brains show that Tet3 interacts in the nucleus directly with selected enzymes of the mitochondrial citric acid cycle. This leads to the formation of isocitrate. Tet3 also interacts with aspartate aminotransferase, which produces oxaloacetate. Although oxaloacetate and isocitrate are biosynthetic alpha-ketoglutarate precursors, they function as inhibitors of Tet3 and are needed to protect the reactive Fe2+ center from degrading DNA. The supply of Tet3 with alpha-ketoglutarate is established by a direct interaction of Tet3 with glutamate dehydrogenase (Glud1), which converts the neurotransmitter glutamate directly into alpha-ketoglutarate. This links Tet3 function to neural activity.
2021-05-10 | PXD004518 | Pride
Project description:PGC7 is a primordial germ cell (PGCs)-specific protein involved in epigenetic chromatin reprogramming in the zygote following fertilization. TET3 is a dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in epigenetic chromatin reprogramming in the zygote following fertilization. PGC7 participates in protection of DNA methylation in the maternal pronucleus by preventing conversion of 5mC to 5hmC by TET3 oxidization subsequent DNA demethylation. Thus we tested the co-localization of PGC7 and TET3 in specific loci by ChIP-seq assays.
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Project description:TET3 interaction proteoimcs +/- treatment, +/- IgG control. Label free quantitative proteomics on Fusion Lumos MS.
2024-04-16 | PXD045465 | Pride
Project description:To define TET3 function in cell differentiation, we profiled the intestinal epithelium at the single-cell level from wild-type and Tet3 knockout mice. Our works shows that, in the absence of TET3, enterocytes exhibit an aberrant differentiation trajectory and do not acquire a physiological cell identity due to an impairment in oxidative phosphorylation, specifically due to the reduced expression of genes encoding for ATP synthase membrane domain subunits. To assess whether the downregulation of ATP synthase subunits upon TET3 loss was due to a TET3 catalytic or non-catalytic activity, we examined global DNA methylation patterns in wild-type and Tet3 knockout intestinal epithelium by whole-genome bisulfite sequencing (WGBS). Our results show that these critical ATP synthase subunits coding-genes did not show any hyperDMR in their regulatory regions, excluding TET3 catalytic activity as the mechanism underlying their decreased gene expression and, pointing thus to TET3 non-catalytic activity.
2024-10-22 | GSE274671 | GEO
Project description:To study the role of tet3 and 5-hydroxymethylation in mouse intestine homeostasis our objectives are: To determine the cell types that show a 5hmC reduction level in the absence of Tet3. Identify the role of Tet3 on transcriptional regulation in the small intestinal epithelium. Define the physiological functions impaired in Tet3 -/- small intestine epithelium.
2024-10-22 | GSE171368 | GEO
Project description:The TET3 CXXC domain has unique DNA binding properties. It binds to DNA in a cytosine-dependent manner that prefers binding to CpG dinucleotides but is not restricted by the CpG-content, distinct from other well-characterized CXXC domains. To map the TET3 CXXC domain binding sites across the human genome, we purified the GST-tagged TET3 CXXC domain protein and performed the GST pull-down assay using the genomic DNA purified from HEK293T cells. The enriched DNA fragments were then sequenced and aligned to human genome(hg19). We used the GST pull-down assay followed by DNA deep sequencing to map the DNA bound by the TET3 CXXC domain in vitro.
2012-12-10 | E-GEOD-41551 | biostudies-arrayexpress
Project description:We compared TET1 and TET3 overexpressing cells to uninduced cells with endogenous levels of the respective transcript to determine global gene expression changes. TET1 overexpression, TET3 overexpression
2015-07-16 | E-GEOD-39186 | biostudies-arrayexpress
Project description:DNA demethylation of paternal genome in zygotes takes place in various mammals including mice and human. Recent studies have revealed that this is achieved through Tet3-mediated iterative oxidation of 5-methylcytosine (5mC) coupled with replication-dependent dilution. Tet3-mediated paternal DNA demethylation is believed to be required for mouse development given that Tet3 heterozygous embryos, derived by fertilizing Tet3 knockout (KO) oocytes with wild-type (WT) sperms, exhibit 5mC oxidation defects and embryonic sublethality, Here we demonstrate that the sublethality phenotype of the maternal KO mice is caused by haploinsufficiency of Tet3, but not by defective paternal 5mC oxidation. We found that Tet3 heterozygous mice derived from crosses of heterozygous father or mother with WT mice also exhibit sublethality phenotype similarly to Tet3 maternal KO mice. Importantly, embryos reconstituted with WT paternal nuclei that bypassed 5mC oxidation develop to term and grow to adulthood normally. Genome-scale DNA methylation analysis of the maternal KO zygotes and blastocysts demonstrated that hypermethylation caused by the depletion of maternal Tet3 is largely diminished by the blastocyst stage. Our study thus not only demonstrates that Tet3-mediated paternal 5mC oxidation is dispensable for mouse development but also suggests the existence of a compensation mechanism in preimplantation embryos that can compensate for the defective 5mC oxidation in zygotes. This data set includes RRBS data of wild-type and maternal Tet3 KO zygotes and blastocysts (C57BL/6J x CAST/EiJ)
2015-02-28 | E-GEOD-62719 | biostudies-arrayexpress
Project description:To gain a mechanistic insight into TET3-mediated regulation of muscle insulin sensitivity, we performed genome-wide expression profiling (RNA-seq) on RNA isolated from GAS muscles of muscle TET3 specific knockdown mice and WT littermates.
2023-12-05 | GSE224042 | GEO