ArticleThe Journal of biological chemistry2002
Role of de novo DNA methyltransferases and methyl CpG-binding proteins in gene silencing in a rat hepatoma.
Article in The Journal of biological chemistry, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 24 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
24 citing papers in PubMed, 53 citations in OpenAlex.
- Mutual regulation of microRNAs and DNA methylation in human cancers.Epigenetics · 2017Review
- Androgen receptor is negatively correlated with the methylation-mediated transcriptional repression of miR-375 in human prostate cancer cells.Oncology reports · 2014Article
- Hypothermia enhances induction of protective protein metallothionein under ischemia.Journal of neuroinflammation · 2013Article
- Article
- Reduced susceptibility of DNA methyltransferase 1 hypomorphic (Dnmt1N/+) mice to hepatic steatosis upon feeding liquid alcohol diet.PloS one · 2012Article
- Novel Insights into the Molecular Mechanism of Action of DNA Hypomethylating Agents: Role of Protein Kinase C δ in Decitabine-Induced Degradation of DNA Methyltransferase 1.Genes & cancer · 2012Article
- DNA methyltransferase controls stem cell aging by regulating BMI1 and EZH2 through microRNAs.PloS one · 2011Article
- Methylation of histone H3 and H4 by PRMT5 regulates ribosomal RNA gene transcription.Journal of cellular biochemistry · 2010Article
- A new class of quinoline-based DNA hypomethylating agents reactivates tumor suppressor genes by blocking DNA methyltransferase 1 activity and inducing its degradation.Cancer research · 2009Article
- Methylation mediated silencing of MicroRNA-1 gene and its role in hepatocellular carcinogenesis.Cancer research · 2008Article
- Downregulation of miR-122 in the rodent and human hepatocellular carcinomas.Journal of cellular biochemistry · 2006Article
- Role of DNA methyltransferases in regulation of human ribosomal RNA gene transcription.The Journal of biological chemistry · 2006Article
- A folate- and methyl-deficient diet alters the expression of DNA methyltransferases and methyl CpG binding proteins involved in epigenetic gene silencing in livers of F344 rats.The Journal of nutrition · 2006Article
- Identification of T-cadherin as a novel target of DNA methyltransferase 3B and its role in the suppression of nerve growth factor-mediated neurite outgrowth in PC12 cells.The Journal of biological chemistry · 2006Article
- Article
- Physical and functional interaction of DNA methyltransferase 3A with Mbd3 and Brg1 in mouse lymphosarcoma cells.Cancer research · 2005Article
- Epigenetic regulation of protein tyrosine phosphatases: potential molecular targets for cancer therapy.Cancer gene therapy · 2005Review
- 5-Aza-deoxycytidine induces selective degradation of DNA methyltransferase 1 by a proteasomal pathway that requires the KEN box, bromo-adjacent homology domain, and nuclear localization signal.Molecular and cellular biology · 2005Article
- Article
- DNA methyltransferase 3b regulates nerve growth factor-induced differentiation of PC12 cells by recruiting histone deacetylase 2.Molecular and cellular biology · 2005Article
Corrections and comments
- Retraction · 2018-07-19Concerns/Issues about Data · Concerns/Issues about Image ·
- RetractedRole of2018
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The expression of metallothionein-I (MT-I), a known antioxidant, was suppressed in a transplanted rat hepatoma because of promoter methylation and was induced by heavy metals only after demethylation by 5-azacytidine (5-AzaC). Treatment of the tumor-bearing rats with 5-AzaC resulted in significant regression of the hepatoma. When the inhibitor-treated tumor was allowed to grow in a new host, MT-I promoter was remethylated, which suggested de novo methylation. The activities of both de novo (3-fold) and maintenance DNA methyltransferases (DNMT) (5-fold) were higher in the hepatoma than in the host liver. The mRNA levels of the de novo methyltransferases DNMT3a and DNMT3b were 3- and 6-fold higher, respectively, in the tumor implicating transcriptional up-regulation of these two genes in this tissue. Immunohistochemical analysis showed exclusive localization of DNMT3a in the nuclei of both the liver and hepatoma, whereas DNMT3b was detected in the nuclei as well as the cytoplasm. Immunoblot assay showed that the levels of DNMT1, DNMT3a, and DNMT3b proteins in the hepatoma were 5-, 10-, and 4-fold higher, respectively, than in the liver. The mRNA level of the major methyl CpG-binding protein (MeCP2) was 8-fold higher in the tumor compared with the liver. Immunohistochemical studies showed that MeCP2 is localized exclusively in the nuclei of both tissues. A chromatin immunoprecipitation assay demonstrated that MeCP2 was associated with the MT-I promoter in the hepatoma implicating its involvement in repressing the methylated promoter. Analysis of the DNA isolated from the liver and hepatoma by RLGS-M (restriction landmark genomic scanning with methylation-sensitive enzyme) (NotI) showed that many genes in addition to MT-I were methylated in the hepatoma. These data demonstrate suppression of the MT-I gene and probably other genes in a solid tumor by promoter methylation and have provided potential molecular mechanisms for the altered methylation profile of the genes in this tumor.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.