ArticleProceedings of the National Academy of Sciences of the United States of America2001
Overexpression of 5-methylcytosine DNA glycosylase in human embryonic kidney cells EcR293 demethylates the promoter of a hormone-regulated reporter gene.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 78 citations in OpenAlex.
- Multi-omics Analysis of Primary Cell Culture Models Reveals Genetic and Epigenetic Basis of Intratumoral Phenotypic Diversity.Genomics, proteomics & bioinformatics · 2019Article
- Recent advances in mammalian protein production.FEBS letters · 2014Review
- Specific transcriptional enhancement of inducible nitric oxide synthase by targeted promoter demethylation.Epigenetics · 2013Article
- Review
- Base excision repair facilitates a functional relationship between Guanine oxidation and histone demethylation.Antioxidants & redox signaling · 2013Review
- Advances in Mammalian cell line development technologies for recombinant protein production.Pharmaceuticals (Basel, Switzerland) · 2013Article
- Transcriptional regulation of thymine DNA glycosylase (TDG) by the tumor suppressor protein p53.Cell cycle (Georgetown, Tex.) · 2012Article
- Epigenetic Editing: targeted rewriting of epigenetic marks to modulate expression of selected target genes.Nucleic acids research · 2012Review
- DNA demethylation by TDG.Epigenomics · 2012Review
- DNA glycosylases: in DNA repair and beyond.Chromosoma · 2012Review
- Active DNA demethylation in plants and animals.Cold Spring Harbor symposia on quantitative biology · 2012Review
- Article
- Embryonic lethal phenotype reveals a function of TDG in maintaining epigenetic stability.Nature · 2011Article
- Endocrine disruptors, environmental oxygen, epigenetics and pregnancy.Frontiers in bioscience (Elite edition) · 2011Review
- Opposing regulatory roles of phosphorylation and acetylation in DNA mispair processing by thymine DNA glycosylase.Nucleic acids research · 2010Article
- Active DNA demethylation mediated by DNA glycosylases.Annual review of genetics · 2009Review
- Active cytosine demethylation triggered by a nuclear receptor involves DNA strand breaks.Proceedings of the National Academy of Sciences of the United States of America · 2006Article
- DEMETER and REPRESSOR OF SILENCING 1 encode 5-methylcytosine DNA glycosylases.Proceedings of the National Academy of Sciences of the United States of America · 2006Article
- Towards understanding the epigenetics of transcription by chromatin structure and the nuclear matrix.Gene therapy & molecular biology · 2005Article
- T:G mismatch-specific thymine-DNA glycosylase (TDG) as a coregulator of transcription interacts with SRC1 family members through a novel tyrosine repeat motif.Nucleic acids research · 2005Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have shown that the DNA demethylation complex isolated from chicken embryos has a G(.)T mismatch DNA glycosylase that also possesses 5-methylcytosine DNA glycosylase (5-MCDG) activity. Herein we show that human embryonic kidney cells stably transfected with 5-MCDG cDNA linked to a cytomegalovirus promoter overexpress 5-MCDG. A 15- to 20-fold overexpression of 5-MCDG results in the specific demethylation of a stably integrated ecdysone-retinoic acid responsive enhancer-promoter linked to a beta-galactosidase reporter gene. Demethylation occurs in the absence of the ligand ponasterone A (an analogue of ecdysone). The state of methylation of the transgene was investigated by Southern blot analysis and by the bisulfite genomic sequencing reaction. Demethylation occurs downstream of the hormone response elements. No genome-wide demethylation was observed. The expression of an inactive mutant of 5-MCDG or the empty vector does not elicit any demethylation of the promoter-enhancer of the reporter gene. An increase in 5-MCDG activity does not influence the activity of DNA methyltransferase(s) when tested in vitro with a hemimethylated substrate. There is no change in the transgene copy number during selection of the clones with antibiotics. Immunoprecipitation combined with Western blot analysis showed that an antibody directed against 5-MCDG precipitates a complex containing the retinoid X receptor alpha. The association between retinoid receptor and 5-MCDG is not ligand dependent. These results suggest that a complex of the hormone receptor with 5-MCDG may target demethylation of the transgene in this system.
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Registered trials
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