Ontology highlight
ABSTRACT:
PROVIDER: PRJNA517055 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10239450_1.fastq.gz | Fastqsanger.gz | |||
| SRR10239450_2.fastq.gz | Fastqsanger.gz | |||
| SRR10239451_1.fastq.gz | Fastqsanger.gz | |||
| SRR10239451_2.fastq.gz | Fastqsanger.gz | |||
| SRR10239452_1.fastq.gz | Fastqsanger.gz |
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Project description:Tet3 converts 5-methylcyotsine to 5-hydroxymethylcytosine (5hmC), although it remains unclear how its functions can be regulated. We showed that Tet3 is phosphorylated by cyclin-dependent kinase 5 at a highly conserved serine residue within its catalytic domain, which leads to an increase in its dioxygenase activity in vitro. Interestingly, when stably expressed in Tet triple-knockout mouse embryonic stem cells (mESCs), wild-type Tet3 elicited higher 5hmC enrichment and expression of genes involved in neurogenesis whereas phosphor-mutant Tet3 caused elevated 5hmC and expression of metabolic pathways genes. Expression of wild-type, but not phosphor-mutant Tet3 in Tet3-knockout mESCs, causes optimal expression of BRN2, Hes1 and Hey2 transcription factors which lead to robust terminal differentiation measured by MAP2 expression. Taken together, our results suggest that cdk5-mediated phosphorylation of Tet3 ensures robust activation of neuronal transcriptional programs during differentiation.
2019-11-29 | GSE130384 | GEO
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:Here we reveal a hierarchical mechanism in the direct conversion of fibroblasts into induced neuronal (iN) cells mediated by the transcription factors Ascl1, Brn2, and Myt1l.
2013-10-24 | GSE43916 | GEO
Project description:Here we reveal a hierarchical mechanism in the direct conversion of fibroblasts into induced neuronal (iN) cells mediated by the transcription factors Ascl1, Brn2, and Myt1l. Examination of global transcriptional changes and mapping genome-wide transcription factors occupancy at distinct time points during the transdifferentiation process
2013-04-10 | E-GEOD-43916 | biostudies-arrayexpress
Project description:Stem cells are a potential key strategy for treating neurodegenerative diseases in which the generation of new neurons is critical. A better understanding of the characteristics and molecular properties of neural stem cells (NSC) and differentiated neurons can help in assessing neuronal maturity and possibly in devising better therapeutic strategies. We have therefore performed an in-depth gene expression profiling study of the C17.2 NSC line and primary neurons (PN) derived from embryonic mouse brains. Microarray analysis revealed a neuron-specific gene expression signature that distinguishes PN from NSCs, with elevated levels of transcripts involved in neuronal functions such as neurite development, axon guidance, in PN. The same comparison revealed decreased levels of multiple cytokine transcripts such as IFN, TNF, TGF, and IL. Among the differentially expressed genes, we found a statistically significant enrichment of genes in the ephrin, neurotrophin, CDK5 and actin pathways which control multiple neuronal-specific functions. Furthermore, genes involved in cell cycle were among the most significantly changed in PN. In order to better understand the role of cell cycle arrest in mediating NSCs differentiation, we blocked the cell cycle of NSCs with Mitomycin C (MMC) and examined cellular morphology and gene expression signatures. Although these MMC-treated NSCs displayed a neuronal morphology and expressed some neuronal differentiation marker genes, their gene expression patterns was very different from primary neurons. We conclude that: 1) Fully differentiated primary neurons display a specific neuronal gene expression signature; 2) cell-cycle block in NSC does not induce the formation of fully differentiated neurons; 3) Cytokines such as IFN, TNF, TGF and IL are part of normal NSC function and/or physiology; 4) Signaling pathways of ephrin, neurotrophin, CDK5 and actin, related to major neuronal features, are dynamically enriched in genes showing changes in expression level. Gene expression profiles in neuronal stem cell, mitomycin-treated neuronal stem cells and primary neuronal cultures were compared to examine cellular morphology and gene expression signatures during neuronal differentiation.
2011-11-28 | E-GEOD-24116 | biostudies-arrayexpress
Project description:<p>Tet3 is the main α-ketoglutarate (αKG)-dependent dioxygenase in neurons that converts 5-methyl-dC into 5-hydroxymethyl-dC and further on to 5-formyl- and 5-carboxy-dC. Neurons possess high levels of 5-hydroxymethyl-dC that further increase during neural activity to establish transcriptional plasticity required for learning and memory functions. How αKG, which is mainly generated in mitochondria as an intermediate of the tricarboxylic acid cycle, is made available in the nucleus has remained an unresolved question in the connection between metabolism and epigenetics. We show that in neurons the mitochondrial enzyme glutamate dehydrogenase, which converts glutamate into αKG in an NAD+-dependent manner, is redirected to the nucleus by the αKG-consumer protein Tet3, suggesting on-site production of αKG. Further, glutamate dehydrogenase has a stimulatory effect on Tet3 demethylation activity in neurons, and neuronal activation increases the levels of αKG. Overall, the glutamate dehydrogenase-Tet3 interaction might have a role in epigenetic changes during neural plasticity.</p><p><br></p>
2021-06-24 | MTBLS2852 | MetaboLights
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:TET enzymes oxidize 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), a process thought to be intermediary in an active DNA demethylation mechanism. Notably, 5hmC is highly abundant in the brain and in neuronal cells. Here we show that Tet3 is highly upregulated during neuronal differentiation and necessary to maintain silencing of pluripotency-associated genes in neural precursor cells (NPCs). Indeed, Tet3 knockdown (KD) in NPCs led to a significant increase in Oct4 and Nanog gene expression, with OCT4-positive cells appearing as cellular aggregates. Moreover, Tet3 KD led to a genome-scale loss of DNA methylation and hypermethylation of a small number of CpGs that are notably located at neurogenesis-related genes and at imprinting control regions (ICRs) of three imprinted genes (Peg10, Zrsr1 and Mcts2). Our results suggest that TET3 plays a pivotal role in maintaining neural stem cell identity and DNA methylation levels in neural precursor cells, and point to a non-catalytic role for TET3 in neural differentiation.
2019-09-23 | GSE123110 | GEO
Project description:Lineage-specific transcriptional regulators control differentiation states not only during normal development but also during cancer evolution. By investigating super-enhancer landscape of lung squamous cell carcinoma (LUSC), we identified a unique ‘neural’ subtype defined by Sox2 and a neural lineage factor Brn2. Robust protein-protein interaction and genomic co-occupancy of these factors indicated their transcriptional cooperation in this ‘neural’ LUSC in contrast to the cooperation of Sox2 and p63 in the classical LUSC. Introduction of p63 expression in the “neural’ LUSC invoked the classical LUSC lineage accompanied by Brn2 downregulation and increased activities of ErbB/Akt and MAPK-ERK pathways. Collectively, our data demonstrate a unique LUSC lineage featured by Sox2 cooperation with Brn2 instead of p63, for which distinct therapeutic approaches may be warranted.
2019-09-17 | GSE137460 | GEO
Project description:Lineage-specific transcriptional regulators control differentiation states not only during normal development but also during cancer evolution. By investigating super-enhancer landscape of lung squamous cell carcinoma (LUSC), we identified a unique ‘neural’ subtype defined by Sox2 and a neural lineage factor Brn2. Robust protein-protein interaction and genomic co-occupancy of these factors indicated their transcriptional cooperation in this ‘neural’ LUSC in contrast to the cooperation of Sox2 and p63 in the classical LUSC. Introduction of p63 expression in the “neural’ LUSC invoked the classical LUSC lineage accompanied by Brn2 downregulation and increased activities of ErbB/Akt and MAPK-ERK pathways. Collectively, our data demonstrate a unique LUSC lineage featured by Sox2 cooperation with Brn2 instead of p63, for which distinct therapeutic approaches may be warranted.
2019-09-17 | GSE137459 | GEO