Evidence map›Paper›PMID 10497224›Full record

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.

S Majumder, K Ghoshal, Z Li, S T Jacob

Open access · hybridAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.8field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 31 citations in OpenAlex.

  1. Regulatory Plasticity of Earthworm wMT-2 Gene Expression.International journal of molecular sciences · 2017
    Article
  2. Article
  3. Article
  4. 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 · 2007
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

S MajumderDepartment of Medical Biochemistry, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA.
K Ghoshal
Z Li
S T Jacob
The Ohio State University · US

Funding

ROLE OF METALLOTHIONEIN IN CANCER AND DRUG RESISTANCER01CA061321 · NCI · ROSALIND FRANKLIN UNIV OF MEDICINE &SCI · PI JACOB, SAMSON T · 1994 to 1998
–
NCI NIH HHS CA 61321NCI NIH HHS R01 CA061321
6 · The paper itself

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.

Indexed as

Antigens, NuclearDNA HelicasesPromoter Regions, GeneticAnimalsAzacitidineBase SequenceCell LineCpG IslandsDNADNA-Binding ProteinsDNA FootprintingDNA MethylationGene ExpressionGene SilencingKu AutoantigenMetallothioneinAntigens, NuclearAzacitidineDNADNA-Binding ProteinsDNA HelicasesKu AutoantigenMetallothioneinNuclear ProteinsXRCC5 protein, humanXrcc6 protein, humanXrcc6 protein, rat

Identifiers

PMID10497224
PMCPMC2276567
OpenAlexW2015199349

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.