Unknown,Transcriptomics,Genomics,Proteomics

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


ABSTRACT: 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.

ORGANISM(S): Mus musculus

SUBMITTER: Fredy Siegrist 

PROVIDER: E-GEOD-20693 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Thymine DNA glycosylase (TDG) is a member of the uracil DNA glycosylase (UDG) superfamily of DNA repair enzymes. Owing to its ability to excise thymine when mispaired with guanine, it was proposed to act against the mutability of 5-methylcytosine (5-mC) deamination in mammalian DNA. However, TDG was also found to interact with transcription factors, histone acetyltransferases and de novo DNA methyltransferases, and it has been associated with DNA demethylation in gene promoters following activat  ...[more]

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