ArticleThe Journal of biological chemistry1999
Hypermethylation of metallothionein-I promoter and suppression of its induction in cell lines overexpressing the large subunit of Ku protein.
Article in The Journal of biological chemistry, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 31 citations in OpenAlex.
- Regulatory Plasticity of Earthworm wMT-2 Gene Expression.International journal of molecular sciences · 2017Article
- Loss of metallothionein predisposes mice to diethylnitrosamine-induced hepatocarcinogenesis by activating NF-kappaB target genes.Cancer research · 2010Article
- Estrogen-mediated suppression of the gene encoding protein tyrosine phosphatase PTPRO in human breast cancer: mechanism and role in tamoxifen sensitivity.Molecular endocrinology (Baltimore, Md.) · 2009Article
- Methylation and silencing of protein tyrosine phosphatase receptor type O in chronic lymphocytic leukemia.Clinical cancer research : an official journal of the American Association for Cancer Research · 2007Article
- Article
- Physical and functional interaction of DNA methyltransferase 3A with Mbd3 and Brg1 in mouse lymphosarcoma cells.Cancer research · 2005Article
- Article
- Protein tyrosine phosphatase receptor-type O (PTPRO) exhibits characteristics of a candidate tumor suppressor in human lung cancer.Proceedings of the National Academy of Sciences of the United States of America · 2004Article
- Role of human ribosomal RNA (rRNA) promoter methylation and of methyl-CpG-binding protein MBD2 in the suppression of rRNA gene expression.The Journal of biological chemistry · 2004Article
- Suppression of the protein tyrosine phosphatase receptor type O gene (PTPRO) by methylation in hepatocellular carcinomas.Oncogene · 2003Article
- Chromium(VI) down-regulates heavy metal-induced metallothionein gene transcription by modifying transactivation potential of the key transcription factor, metal-responsive transcription factor 1.The Journal of biological chemistry · 2003Article
- Inhibitors of histone deacetylase and DNA methyltransferase synergistically activate the methylated metallothionein I promoter by activating the transcription factor MTF-1 and forming an open chromatin structure.Molecular and cellular biology · 2002Article
- Suppression of metallothionein-I/II expression and its probable molecular mechanisms.Environmental health perspectives · 2002Article
- Role of de novo DNA methyltransferases and methyl CpG-binding proteins in gene silencing in a rat hepatoma.The Journal of biological chemistry · 2002Article
- Influenza virus infection induces metallothionein gene expression in the mouse liver and lung by overlapping but distinct molecular mechanisms.Molecular and cellular biology · 2001Article
- Downregulation of constitutive and heavy metal-induced metallothionein-I expression by nuclear factor I.Gene expression · 2001Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
We have shown previously that the heavy metal-induced metallothionein-I (MT-I) gene expression is specifically repressed in a rat fibroblast cell line (Ku-80) overexpressing the 80-kDa subunit of Ku autoantigen but not in cell lines overexpressing the 70-kDa subunit or Ku heterodimer. Here, we explored the molecular mechanism of silencing of MT-I gene in Ku-80 cells. Genomic footprinting analysis revealed both basal and heavy metal-inducible binding at specific cis elements in the parental cell line (Rat-1). By contrast, MT-I promoter in Ku-80 cells was refractory to any transactivating factors, implying alteration of chromatin structure. Treatment of two clonal lines of Ku-80 cells with 5-azacytidine, a potent DNA demethylating agent, rendered MT-I gene inducible by heavy metals, suggesting that the gene is methylated in these cells. Bisulfite genomic sequencing revealed that all 21 CpG dinucleotides in MT-I immediate promoter were methylated in Ku-80 cells, whereas only four CpG dinucleotides were methylated in Rat-1 cells. Almost all methylated CpG dinucleotides were demethylated in Ku-80 cells after 5-azacytidine treatment. To our knowledge, this is the first report that describes hypermethylation of a specific gene promoter and its resultant silencing in response to overexpression of a cellular protein.
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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.