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A low-complexity domain of Tet3 dioxygenase shields the oocyte methylome from oxidative erosion

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE222501 | GEO | 2023/08/24

REPOSITORIES: GEO

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A low-complexity domain of Tet3 dioxygenase shields the oocyte methylome from oxidative erosion [RNA-seq]

Project description:Dynamic DNA methylation and demethylation regulate gene expression during development. While DNA methyltransferases (DNMTs) establish and maintain cytosine methylation patterns, Ten-eleven translocation (Tet) dioxygenases catalyze sequential oxidation of 5-methylcytosine (5mC) to promote demethylation. Target-specific 5mC oxidation requires precise regulation of the Tet enzymatic activity. However, the mechanism underlying their activity control remains largely unexplored. Here we show a large low-complexity domain (LCD), present within the catalytic domain of Tet3, functions to repress the dioxygenase activity. Recombinant LCD-deleted Tet3 exhibits enhanced activity to convert 5mC into oxidized species. Deletion of the Tet3 LCD in mouse oocytes renders 5mC oxidation indiscriminately across the genome, leading to most prominently the derepression of ERVK retrotransposons and upregulation of adjacent genes. The extensive 5mC oxidation is associated with impairments in oocyte development. These findings suggest an intrinsic auto-regulatory mechanism of Tet3 dioxygenase operating to ensure a tight regulation of its enzymatic activity to achieve spatiotemporal specificity of methylome reprogramming during oocyte development.

2023-08-24 | GSE222500 | GEO

A low-complexity domain of Tet3 dioxygenase shields the oocyte methylome from oxidative erosion [BiSulfite-seq]

2023-08-24 | GSE222498 | GEO

A low-complexity domain of Tet3 dioxygenase shields the oocyte methylome from oxidative erosion [ ACE-seq]

2023-08-24 | GSE222492 | GEO

A low-complexity domain of Tet3 dioxygenase shields the oocyte methylome from oxidative erosion

Project description:A low-complexity domain of Tet3 dioxygenase shields the oocyte methylome from oxidative erosion

| PRJNA922212 | ENA

A low-complexity domain of Tet3 dioxygenase shields the oocyte methylome from oxidative erosion [BiSulfite-seq]

Project description:A low-complexity domain of Tet3 dioxygenase shields the oocyte methylome from oxidative erosion [BiSulfite-seq]

| PRJNA922209 | ENA

A low-complexity domain of Tet3 dioxygenase shields the oocyte methylome from oxidative erosion [ ACE-seq]

Project description:A low-complexity domain of Tet3 dioxygenase shields the oocyte methylome from oxidative erosion [ ACE-seq]

| PRJNA922211 | ENA

A low-complexity domain of Tet3 dioxygenase shields the oocyte methylome from oxidative erosion [RNA-seq]

Project description:A low-complexity domain of Tet3 dioxygenase shields the oocyte methylome from oxidative erosion [RNA-seq]

| PRJNA922216 | ENA

Tet3 CXXC domain and dioxygenase activity cooperatively regulate key genes for Xenopus eye and neural development.

Project description:Ten-Eleven Translocation (Tet) family of dioxygenases dynamically regulates DNA methylation and has been implicated in cell lineage differentiation and oncogenesis. Yet their functions and mechanisms of action in gene regulation and embryonic development are largely unknown. Here, we report that Xenopus Tet3 plays an essential role in early eye and neural development by directly regulating a set of key developmental genes. Tet3 is an active 5mC hydroxylase regulating the 5mC/5hmC status at target gene promoters. Biochemical and structural studies further demonstrate that the Tet3 CXXC domain is critical for specific Tet3 targeting. Finally, we show that the enzymatic activity and CXXC domain are both crucial for Tet3's biological function. Together, these findings define Tet3 as a transcription regulator and reveal a molecular mechanism by which the 5mC hydroxylase and DNA binding activities of Tet3 cooperate to control target gene expression and embryonic development.

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Intrinsic and extrinsic connections of Tet3 dioxygenase with CXXC zinc finger modules.

Project description:Tet proteins are emerging as major epigenetic modulators of cell fate and plasticity. However, little is known about how Tet proteins are targeted to selected genomic loci in distinct biological contexts. Previously, a CXXC-type zinc finger domain in Tet1 was shown to bind CpG-rich DNA sequences. Interestingly, in human and mouse the Tet2 and Tet3 genes are adjacent to Cxxc4 and Cxxc10-1, respectively. The CXXC domains encoded by these loci, together with those in Tet1 and Cxxc5, identify a distinct homology group within the CXXC domain family. Here we provide evidence for alternative mouse Tet3 transcripts including the Cxxc10-1 sequence (Tet3(CXXC)) and for an interaction between Tet3 and Cxxc4. In vitro Cxxc4 and the isolated CXXC domains of Tet1 and Tet3(CXXC) bind DNA substrates with similar preference towards the modification state of cytosine at a single CpG site. In vivo Tet1 and Tet3 isoforms with and without CXXC domain hydroxylate genomic 5-methylcytosine with similar activity. Relative transcript levels suggest that distinct ratios of Tet3(CXXC) isoforms and Tet3-Cxxc4 complex may be present in adult tissues. Our data suggest that variable association with CXXC modules may contribute to context specific functions of Tet proteins.

| S-EPMC3653909 | biostudies-literature

Erosion reduces soil microbial diversity, network complexity and multifunctionality.

Project description:While soil erosion drives land degradation, the impact of erosion on soil microbial communities and multiple soil functions remains unclear. This hinders our ability to assess the true impact of erosion on soil ecosystem services and our ability to restore eroded environments. Here we examined the effect of erosion on microbial communities at two sites with contrasting soil texture and climates. Eroded plots had lower microbial network complexity, fewer microbial taxa, and fewer associations among microbial taxa, relative to non-eroded plots. Soil erosion also shifted microbial community composition, with decreased relative abundances of dominant phyla such as Proteobacteria, Bacteroidetes, and Gemmatimonadetes. In contrast, erosion led to an increase in the relative abundances of some bacterial families involved in N cycling, such as Acetobacteraceae and Beijerinckiaceae. Changes in microbiota characteristics were strongly related with erosion-induced changes in soil multifunctionality. Together, these results demonstrate that soil erosion has a significant negative impact on soil microbial diversity and functionality.

| S-EPMC8319411 | biostudies-literature

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