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HMeDIP-Seq of Tet2 knockout hippocampal neurons

ABSTRACT: hMeDIP-Seq of Tet2 knockout hippocampal neurons

PROVIDER: PRJNA820784 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18506434_1.fastq.gz	Fastqsanger.gz
	SRR18506434_2.fastq.gz	Fastqsanger.gz
	SRR18506435_1.fastq.gz	Fastqsanger.gz
	SRR18506435_2.fastq.gz	Fastqsanger.gz
	SRR18506436_1.fastq.gz	Fastqsanger.gz

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hMeDIP-Seq of Tet2 overexpressing hippocampal neurons

Project description:hMeDIP-Seq of Tet2 overexpressing hippocampal neurons

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hMeDIP-Seq of Tet2 knockout hippocampal neurons

Project description:Tet2 regulates gene expression by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine. Profiling the genomic locations of 5-hydroxymethylcytosine after Tet2 manipulation can inform us of the targets of Tet2 regulation. We profiled hydroxymethylcytosine in Tet2 knockout neurons to determine the targets of Tet2 in neurons.

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Project description:Tet2 regulates gene expression by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine. Profiling the genomic locations of 5-hydroxymethylcytosine after Tet2 manipulation can inform us of the targets of Tet2 regulation. We profiled hydroxymethylcytosine in Tet2 ovexpressing neurons to determine the targets of Tet2 in neurons.

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Loss of neuronal Tet2 enhances hippocampal-dependent cognitive function

Project description:DNA methylation has emerged as a critical modulator of neuronal plasticity and cognitive function. Notwithstanding, the role of enzymes that demethylate DNA remain to be fully explored. Here, we report that loss of ten-eleven translocation methylcytosine dioxygenase 2 (Tet2), which catalyzes oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), in adult neurons enhances cognitive function. In the adult mouse hippocampus, we detected an enrichment of Tet2 in neurons. Viral-mediated neuronal overexpression and RNA interference of Tet2 altered dendritic complexity and synaptic-plasticity-related gene expression in vitro. Overexpression of neuronal Tet2 in adult hippocampus, and loss of Tet2 in adult glutamatergic neurons, resulted in differential hydroxymethylation associated with genes involved in synaptic transmission. Functionally, overexpression of neuronal Tet2 impaired hippocampal-dependent memory, while loss of neuronal Tet2 enhanced memory. Ultimately, these data identify neuronal Tet2 as a molecular target to boost cognitive function.

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LOSS OF NEURONAL TET2 ENHANCES HIPPOCAMPAL-DEPENDENT COGNITIVE FUNCTION

Project description:Chromatin methylation has emerged as a critical modulator of neuronal plasticity and cognitive function. Notwithstanding, the role of enzymes that demethylate DNA remain to be fully explored. Here we report that loss of ten eleven translocation methylcytosine dioxygenase 2 (Tet2), which catalyzes oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), in adult neurons enhances cognitive function. In the adult mouse hippocampus, we detected an enrichment of Tet2 in neurons. Abrogation of neuronal Tet2 in vitro altered synaptic-plasticity related gene expression. We observed that loss of Tet2 in mature glutamatergic neurons in adult mice resulted in differential hydroxymethylation on genes involved in synaptic transmission in the hippocampus. Correspondingly, RNA sequencing identified changes in both long-term potentiation pathways and immune-related genes linked to synaptic plasticity. Functionally, loss of neuronal Tet2 improved performance on hippocampal-dependent spatial and associative memory tasks. Ultimately, this work identifies neuronal Tet2 as a molecular target to enhance cognitive function.

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Rat hippocampal neurons' proteomes

Project description:We induced over-expression and under-expression of Camk2b in cultured rat hippocampal neurons through transfection with lentivirus plasmids. Then isobaric tag for relative and absolute quantitation (iTRAQ)-based quantitative proteomics followed by bioinformatics analyses were carried out to explore the impacts of Camk2b dysexpression on the proteome of the neurons.

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Tet2 negatively regulates memory fidelity

Project description:Tet2 functions in the CA1 as a negative regulator of long-term memory, and its haploinsufficiency in glutamatergic neurons or knockdown across the CA1 in mice is sufficient to enhance the fidelity of hippocampal-dependent spatial and associative memory.

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Regulation of host antiviral factors expression by TET2-mediated DNA demethylation

Project description:Host antiviral innate immune response is regulated by epigenetic mechanisms. TET2 oxidizes the methyl group of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in a process that activates demethylation of CpG DNA. Here, we characterize the genome-wide distribution of 5hmC in both wild-type and TET2-knockout THP-1 cells infected with the influenza A virus (IAV) using DNA immunoprecipitation by anti-5hmc antibody coupled with high-throughput DNA sequencing. 5hmC marks signature genes associated with host innate immune response against IAV infection. Moreover, TET2 expression is inhibited by IAV infection via viral endoribonuclease PA-X . Deletion of the TET2 gene in THP-1 cells decreased expression of genes related to interferon signaling. We further verified that TET2 plays a critical role in the expression of STAT1 and some interferon-stimulated genes through demethylation. Collectively, our findings demonstrate a key role of TET2-mediated active DNA demethylation in anti-IAV immunity. Hydroxymethylated DNA immunoprecipitation-sequencing (hMeDIP-Seq) in IAV-infected wild-type and TET2-knockout THP-1 cells.

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Project description:Detect overall RNA level change under TET2 knockout in response to IFNγ. Loss of TET2 alters IFNγ transcriptome, TET2 mediates the IFNγ signaling pathway.

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Gene expression profiles of Tet1 knockout (T1KO), Tet2 knockout (T2KO) and Tet1/Tet2 double knockout (DKO) mouse embryonic stem cells.

Project description:Global gene expression profile of single and double mutant mouse ES cells were compared to wt ES cells. Two male Tet1 KO, one male Tet2 KO, two male double KO, two female double KO, two male WT and two female WT mouse ES cells were compared. Global gene expression profile of single and double knockout mouse embryonic stem cells were compared to that of wild type mouse ES cells. All used ES lines were derived from C57/BL/6 mixed background mice. RNA from feeder free mutant mouse ES cells was competetively hybridized against RNA from WT ES cells. Same sex lines were compared. Two independent ES line of each genotype were used, with the exception of Tet2 KO ES cells where only one male line was used.

2013-02-01 | E-GEOD-42991 | biostudies-arrayexpress

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