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GADD45 promotes locus specific DNA demethylation and 2C cycling in embryonic stem cells

ABSTRACT: GADD45 promotes locus specific DNA demethylation and 2C cycling in embryonic stem cells

PROVIDER: PRJNA525097 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR3922170.fastq.gz	Fastqsanger.gz
	SRR3922180.fastq.gz	Fastqsanger.gz
	SRR3922190.fastq.gz	Fastqsanger.gz
	SRR3922200.fastq.gz	Fastqsanger.gz
	SRR3922171.fastq.gz	Fastqsanger.gz

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GADD45 promotes locus specific DNA demethylation and 2C cycling in embryonic stem cells

Project description:Mouse embryonic stem cell cultures contain a rare cell population of "2C-like" cells resembling 2-cell embryos, the key stage of zygotic genome activation (ZGA). Little is known about positive regulators of the 2C-like state and 2-cell stage embryos. We found that GADD45 (growth arrest and DNA damage 45) proteins, regulators of TET mediated DNA demethylation, promote both states. This SuperSeries is composed of the SubSeries listed below.

2019-05-31 | GSE127720 | GEO

GADD45 promotes locus-specific DNA demethylation and 2C cycling in embryonic stem cells.

Project description:Mouse embryonic stem cell (ESC) cultures contain a rare cell population of "2C-like" cells resembling two-cell embryos, the key stage of zygotic genome activation (ZGA). Little is known about positive regulators of the 2C-like state and two-cell stage embryos. Here we show that GADD45 (growth arrest and DNA damage 45) proteins, regulators of TET (TET methylcytosine dioxygenase)-mediated DNA demethylation, promote both states. Methylome analysis of Gadd45a,b,g triple-knockout (TKO) ESCs reveal locus-specific DNA hypermethylation of ∼7000 sites, which are enriched for enhancers and loci undergoing TET-TDG (thymine DNA glycosylase)-mediated demethylation. Gene expression is misregulated in TKOs, notably upon differentiation, and displays signatures of DNMT (DNA methyltransferase) and TET targets. TKOs manifest impaired transition into the 2C-like state and exhibit DNA hypermethylation and down-regulation of 2C-like state-specific genes. Gadd45a,b double-mutant mouse embryos display embryonic sublethality, deregulated ZGA gene expression, and developmental arrest. Our study reveals an unexpected role of GADD45 proteins in embryonic two-cell stage regulation.

| S-EPMC6601511 | biostudies-literature

Gene expression changes in GADD45 deficient 2-cell mouse embryos

Project description:To study the role of GADD45 proteins in early mouse development, RNA-seq expression profiling was performed with Gadd45a/Gadd45b double knockout (DKO) and wild-type (WT) mouse embryos at 2-cell stage (2C).

2019-05-31 | GSE127719 | GEO

Methylome profiling of GADD45 deficient mouse embryonic stem cells

Project description:In order to study the physiological impact of GADD45 proteins on DNA methylation, we compared the methylation levels of Gadd45a,b,g triple knockout (TKO) and wild-type (Control) mouse embryonic stem cells (mESC) via whole genome bisulfite sequencing (WGBS).

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Expression data from 2C::tomato+ vs 2C::tomato - ES cells

Project description:We compared gene expression from 2C::tomato+/- ES cells from Kdm1a wt and mutant ES cultures 2C::tomato- samples 1, 5, 9 2C::tomato+ samples 2, 6, 10 We collecteded 3 replicates of RNA from 2C::tomato+ and - ES cells

2012-06-17 | E-GEOD-33763 | biostudies-arrayexpress

Gadd45a promotes DNA demethylation through TDG

Project description:Growth arrest and DNA-damage-inducible protein 45 (Gadd45) family members have been implicated in DNA demethylation in vertebrates. However, it remained unclear how they contribute to the demethylation process. Here, we demonstrate that Gadd45a promotes active DNA demethylation through thymine DNA glycosylase (TDG) which has recently been shown to excise 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) generated in Ten-eleven-translocation (Tet) -initiated oxidative demethylation. The connection of Gadd45a with oxidative demethylation is evidenced by the enhanced activation of a methylated reporter gene in HEK293T cells expressing Gadd45a in combination with catalytically active TDG and Tet. Gadd45a interacts with TDG physically and increases the removal of 5fC and 5caC from genomic and transfected plasmid DNA by TDG. Knockout of both Gadd45a and Gadd45b from mouse ES cells leads to hypermethylation of specific genomic loci most of which are also targets of TDG and show 5fC enrichment in TDG-deficient cells. These observations indicate that the demethylation effect of Gadd45a is mediated by TDG activity. This finding thus unites Gadd45a with the recently defined Tet-initiated demethylation pathway. The dataset includes RRBS anlysis of 2 WT ES cell samples and 2 Gadd45a/b DKO ES cell samples.

2015-05-07 | E-GEOD-62496 | biostudies-arrayexpress

Methylome profiling of GADD45 deficient mouse embryonic stem cells

Project description:Methylome profiling of GADD45 deficient mouse embryonic stem cells

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Gadd45a promotes DNA demethylation through TDG

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Expression data from 2C::tomato+ vs 2C::tomato - ES cells

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2012-06-18 | GSE33763 | GEO

mRNA-Seq of 2C::tomato+ vs. - ES cells

Project description:We identified/quantified genes and repeat elements enriched within 2C::tomato+ cells vs. 2C::tomato - cells 2C::tomato + and - cells were collected by FACS for RNA-Seq analysis

2012-06-18 | E-GEOD-33920 | biostudies-arrayexpress

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