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High throughput RNA sequencing of hepatocellular carcinoma and pre tumor samples from Tdg fl/-; UBC-cre/ERT2+ mice livers and their age/sex matched Tdg fl/fl controls livers

ABSTRACT: We isolated whole livers from male TDG knockout livers (4-month post tamoxifen injection) and HCC, along with their age matched male control livers. RNA was extracted from the samples as per RNAzol manufacturer guidelines with DNase treatment. RNA was then analyzed by bioanalyzer and subjected to sequencing using the Illumina NextSeq 500 platform.

ORGANISM(S): Mus musculus

PROVIDER: GSE146401 | GEO | 2020/03/06

REPOSITORIES: GEO

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High throughput RNA sequencing of hepatocellular carcinoma and pre tumor samples from Tdg fl/-; UBC-cre/ERT2+ mice livers and their age/sex matched Tdg fl/fl controls livers

Project description:High throughput RNA sequencing of hepatocellular carcinoma and pre tumor samples from Tdg fl/-; UBC-cre/ERT2+ mice livers and their age/sex matched Tdg fl/fl controls livers

| PRJNA610508 | ENA

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

Gadd45a promotes DNA demethylation through TDG

2015-05-07 | GSE62496 | GEO

Transcription profiling of Mus musculus genotypes Tdg WT vs. Tdg KO

Project description:comparison of Tdg wild type and knockout mouse embryo fibroblast lines

2011-03-07 | E-MEXP-2610 | biostudies-arrayexpress

Thymine DNA glycosylase (TDG) regulates cell cycle–driven p53 transcriptional control in pluripotent cells

Project description:Cell cycle progression is linked to transcriptome dynamics and variations in the response of pluripotent cells to differentiation cues, through mostly unknown determinants. Here, we characterized the cell cycle–associated transcriptome and proteome of mouse embryonic stem cells (mESCs) in naïve ground state. We found that the thymine DNA glycosylase (TDG) is a cell cycle–regulated co-factor of the tumour suppressor p53. Further, TDG and p53 co-bind ESC-specific cis-regulatory elements and thereby control transcription of p53-dependent genes during self-renewal. We determined that the dynamic expression of TDG is required to promote the cell cycle–associated transcriptional heterogeneity. Moreover, we demonstrated that transient depletion of TDG influences cell fate decisions during the early differentiation of mESCs. Our findings reveal an unanticipated role of TDG in promoting molecular heterogeneity during the cell cycle, and highlight the central role of protein dynamics for the temporal control of cell fate during development.

2023-07-31 | PXD029596 | Pride

Effects of Tdg deficiency on overall transcription in mouse embryonic fibroblasts and during cell differentiation

Project description:Because it excises thymine from GM-bM-^@M-"T mismatches, TDG was proposed to counter mutagenesis by 5-methylcytosine deamination. Yet, TDG was also observed to attack 5-methycytosine itself, making it a candidate DNA demethylase, and interactions with transcription factors implicated additional functions in gene regulation. Unlike other DNA glycosylases, TDG is essential for embryonic development. Fibroblasts from Tdg null embryos show massively impaired gene regulation, and this correlates with imbalanced histone modification and CpG methylation. TDG associates with the promoters of affected genes in MEFs and in embryonic stem cells, but epigenetic aberrations appear only in differentiated cells. TDG also contributes to the maintenance of active and bivalent chromatin during cell differentiation, using its DNA glycosylase activity to counter aberrant de novo methylation. Thus, TDG dependent DNA repair stabilizes epigenetic states during cell differentiation. Comparison of 3 Tdg+/- MEF replicates with 3 Tdg-/- MEF replicates. Comparison of Tdg+/- and Tdg-/- ES cells and respective in vitro differentiated neuronal progenitors. Each condition is represented by 3 replicas.

2011-01-31 | E-GEOD-20693 | biostudies-arrayexpress

Profiling of hepatic progenitor cells isolated from Egfr fl/fl and Met fl/fl murine control livers

Project description:Transcriptomic profiling; Determination of the transcriptomic similarity between Egfr fl/fl and Met fl/fl progenitor cells isolated from excised livers (n=3, each)

2013-09-05 | GSE46981 | GEO

TDG orchestrates ATF4-dependent gene transcription during retinoic acid-induced cell lineage committment

Project description:Cell differentiation during development is associated to large-scale modifications in the methylome that require the engagement of an active DNA demethylation machinery including Ten-Eleven-Translocation enzymes for oxidation of 5-methylcytosine and the T:G mismatch DNA glycosylase (TDG) for removal of the oxidized bases. Despite this well-defined molecular function, the biological output of TDG activity remains elusive. Here we combined transcriptomic and epigenomic approaches in TDG knock-out embryonal carcinoma cells, an epiblast stem-like cell model, to decipher TDG function in pluripotent cells and their retinoic acid-induced differentiated progeny. We determined that TDG activity is balancing differentiation in favor of a neural fate at the expense of a cardiac mesoderm fate. This process is associated with a sustained activity of a large set of ATF4-dependent genes in relation with TDG engagement at the Atf4 gene promoter and in conjunction with a TDG-dependent regulation of the mammalian target of rapamycin complex 1. These observations highlight the central role of TDG in cell differentiation and support a model linking metabolic reprogramming to cell fate acquisition.

2024-03-31 | GSE262587 | GEO

TDG orchestrates ATF4-dependent gene transcription during retinoic acid-induced cell lineage committment

2024-03-19 | GSE261602 | GEO

FLAG-TDG-N140A-CD co-immunoprecipitation in HEK293 cells

Project description:Co-immunoprecipitation expreiment of FLAG-tagged human TDG catalytic domain with N140A mutation (FLAG-TDG-N140A-CD) stably expressed in HEK293 cells, compared to control empty (no FLAG-TDG-N140A-CD) HEK293 cells.

2023-03-09 | MSV000091458 | MassIVE

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