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HIF-1 directly induces TET3 expression to redistribute 5-hydroxymethylcytosine and induce erythroid gene expression in hypoxia [5-hmC]

ABSTRACT: HIF-1 directly induces TET3 expression to redistribute 5-hydroxymethylcytosine and induce erythroid gene expression in hypoxia [5-hmC]

PROVIDER: PRJNA598718 | ENA |

REPOSITORIES: ENA

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HIF-1 directly induces TET3 expression to redistribute 5-hydroxymethylcytosine and induce erythroid gene expression in hypoxia [5-hmC]

Project description:We characterized genome-wide 5-hydroxymerhylcytosine (5-hmC) distribution of CD34+ cells undergoing erythroid differentiation in normoxia vs. hypoxia by chemically labeling 5-hmC followed by pull-down and sequencing (hMe-SEAL). We found that hypoxia increases both the number and the prominance of 5-hmC peaks at each time point, especially at day 7 and 10.

2020-02-01 | GSE142869 | GEO

HIF-1 directly induces TET3 expression to redistribute 5-hydroxymethylcytosine and induce erythroid gene expression in hypoxia

Project description:HIF-1 directly induces TET3 expression to redistribute 5-hydroxymethylcytosine and induce erythroid gene expression in hypoxia

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HIF-1 directly induces TET3 expression to redistribute 5-hydroxymethylcytosine and induce erythroid gene expression in hypoxia [ChIP-seq]

Project description:HIF-1 directly induces TET3 expression to redistribute 5-hydroxymethylcytosine and induce erythroid gene expression in hypoxia [ChIP-seq]

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HIF-1 directly induces TET3 expression to redistribute 5-hydroxymethylcytosine and induce erythroid gene expression in hypoxia [RNA-seq]

Project description:HIF-1 directly induces TET3 expression to redistribute 5-hydroxymethylcytosine and induce erythroid gene expression in hypoxia [RNA-seq]

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HIF-1 directly induces TET3 expression to redistribute 5-hydroxymethylcytosine and induce erythroid gene expression in hypoxia [ChIP-seq]

Project description:We performed HIF-1alpha ChIP-seq in K562 cells cultured in normoxia vs. hypoxia for 3 days. We identified two new HIF binding sites in TET3 intron 2 that control TET3 expression in hypoxia

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Rest recruits neuronal Tet3 to induce chromatin remodeling and gene expression

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

Comprehensive mapping of 5-hmC epigenetic dynamics in axon regeneration

Project description:In contrast to CNS neurons, dorsal root ganglia (DRG) neurons can switch to a regenerative state after peripheral axotomy. In a screen for chromatin regulators of the regenerative responses in this conditioning lesion paradigm, we identified Tet methylcytosine dioxygenase 3 (Tet3) as upregulated, along with increased 5-hydroxymethylcytosine (5-hmC) in DRG neurons. We generated genome-wide 5-hmC maps in adult DRG, which demonstrated that peripheral and central axotomy (no regenerative effect) triggered differential 5-hmC changes that are associated with distinct signaling pathways. 5-hmC was altered in half of regeneration-associated genes (RAGs), supporting its role for RAG regulation. Our analyses predicted transcription factors HIF-1, STAT and IRF that may collaborate with Tet3 for 5-hmC modifications. Intriguingly, central axotomy lead to widespread 5-hmC modifications with little overlap with peripheral axotomy, thus potentially constituting a roadblock for regeneration. Our study revealed 5-hmC as a previously unrecognized epigenetic mechanism underlying the divergent responses after axonal injury.

2016-12-09 | GSE85972 | GEO

Redirected nuclear glutamate dehydrogenase supplies Tet3 with a-ketoglutarate in neurons

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

A Model for the Early Diagnosis of Colorectal Cancer by the Detection of 5-hydroxymethylcytosine (5-hmC) in Plasma Cell-free DNA

Project description:In this study, the investigators establish a model for the early diagnosis of colorectal cancer based on detection of 5-hydroxymethylcytosine (5-hmC) in training group and validate the effectiveness of the model using a validation group.

| 2278673 | ecrin-mdr-crc

HIF-1 directly induces TET3 expression to enhance 5-hmC density and induce erythroid gene expression in hypoxia.

Project description: Not available

| S-EPMC7362358 | biostudies-literature