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Role of TET3 in mouse embryonic and adult hematopoiesis [RNA-Seq]

ABSTRACT: In this study: We identified TET3 target genes by transcriptomic profiling of Tet3F/F and Tie2+/cre; Tet3F/F Lin– bone marrow cells by RNA-sequencing.

ORGANISM(S): Mus musculus

PROVIDER: GSE282719 | GEO | 2025/04/22

REPOSITORIES: GEO

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Role of TET3 in mouse embryonic and adult hematopoiesis [EM-Seq]

Project description:In this study: we mapped genome-wide DNA methylation levels in Tet3F/F (control) and cKO Tie2+/cre; Tet3F/F (cKO) Lin– bone marrow cells by enzymatic methyl-sequencing (EM-seq).

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Role of TET3 in mouse embryonic and adult hematopoiesis [E5hmC-seq]

Project description:In this study: we mapped genome-wide DNA hydroxymethylation levels in Tet3F/F (control) and cKO Tie2+/cre; Tet3F/F (cKO) Lin– bone marrow cells by enzymatic 5-hydroxymethylation sequencing (E5hmC-seq).

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Role of TET3 in mouse embryonic and adult hematopoiesis

Project description:This SuperSeries is composed of the SubSeries listed below.

2025-04-22 | GSE282720 | GEO

Tet3 ablation in adult brain neurons increases anxiety-like behavior and regulates cognitive function in mice

Project description:TET3 is a member of the Ten-eleven translocation (TET) family of enzymes which oxidize 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). Tet3 is highly expressed in the brain, where 5hmC levels are most abundant. In adult mice, we observed that TET3 is present in mature neurons and oligodendrocytes but is absent in astrocytes. To investigate the function of TET3 in adult post-mitotic neurons, we crossed Tet3 floxed mice with a neuronal Cre-expressing mouse line, Camk2a-CreERT2, obtaining a Tet3 conditional KO mouse line. Ablation of Tet3 in adult mature neurons resulted in increased anxiety-like behavior with concomitant hypercorticalism, and impaired hippocampal-dependent spatial orientation. Transcriptome and gene-specific expression analysis of the hippocampus showed dysregulation of genes involved in glucocorticoid signaling pathway (HPA axis) in the ventral hippocampus, whereas upregulation of immediate early genes (IEGs) was observed in both dorsal and ventral hippocampal areas. Additionally, Tet3 cKO mice exhibit increased dendritic spine maturation in the ventral CA1 hippocampal subregion. Based on these observations, we suggest that TET3 is involved in molecular alterations, that govern hippocampal-dependent functions. These results reveal a critical role for epigenetic modifications in modulating brain functions, opening new insights into the molecular basis of psychiatric disorders.

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Tet3 KO in lung smooth muscle cells

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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.

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