Evidence map›Paper›PMID 16735507›Full record

ArticleThe Journal of biological chemistry2006

Role of DNA methyltransferases in regulation of human ribosomal RNA gene transcription.

Sarmila Majumder, Kalpana Ghoshal, Jharna Datta, David Spencer Smith, Shoumei Bai, Samson T Jacob

RetractedOpen access · hybridAbstract readRetracted Publication
In one paragraph

Article in The Journal of biological chemistry, 2006. 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 It has been retracted, and should not be counted.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.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.7field-weighted citation impact, top 10% 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

24 citing papers in PubMed, 43 citations in OpenAlex.

  1. Review
  2. Article
  3. The Epigenetic Pathways to Ribosomal DNA Silencing.Microbiology and molecular biology reviews : MMBR · 2016
    Review
  4. Morphology of nuclear transcription.Histochemistry and cell biology · 2016
    Review
  5. Article
  6. Article
  7. Article
  8. Epigenetics of eu- and heterochromatin in inverted and conventional nuclei from mouse retina.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2013
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Structure and function of ribosomal RNA gene chromatin.Biochemical Society transactions · 2008
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Sarmila MajumderDepartment of Molecular and Cellular Biochemistry, College of Medicine, Ohio State University, Columbus, Ohio 43210. Electronic address: majumder.2@osu.edu.
Kalpana GhoshalDepartment of Molecular and Cellular Biochemistry, College of Medicine, Ohio State University, Columbus, Ohio 43210.
Jharna DattaDepartment of Molecular and Cellular Biochemistry, College of Medicine, Ohio State University, Columbus, Ohio 43210.
David Spencer SmithDepartment of Molecular and Cellular Biochemistry, College of Medicine, Ohio State University, Columbus, Ohio 43210.
Shoumei BaiDepartment of Molecular and Cellular Biochemistry, College of Medicine, Ohio State University, Columbus, Ohio 43210.
Samson T JacobDepartment of Molecular and Cellular Biochemistry, College of Medicine, Ohio State University, Columbus, Ohio 43210. Electronic address: jacob.42@osu.edu.
The Ohio State University · US

Funding

MOLECULAR MECHANISMS OF DIET-INDUCED CARCINOGENESISR01CA086978 · NCI · OHIO STATE UNIVERSITY · PI GHOSHAL, KALPANA, JACOB, SAMSON T · 2002 to 2018
$4.9M
DNA METHYLATION AND GENE EXPRESSION IN CANCER CELLSR01ES010874 · NIEHS · OHIO STATE UNIVERSITY · PI JACOB, SAMSON T · 2000 to 2004
$1.6M
NCI NIH HHS CA86978NCI NIH HHS R01 CA086978NIEHS NIH HHS ES10874NIEHS NIH HHS R01 ES010874
6 · The paper itself

Abstract

We have previously demonstrated that the expression of human ribosomal RNA genes (rDNA) in normal and cancer cells is differentially regulated by methylation of the promoter CpG islands. Furthermore, we showed that the methyl CpG-binding protein MBD2 plays a selective role in the methylation-mediated block in rDNA expression. Here, we analyzed the role of three functional mammalian DNA methyltransferases (DNMTs) in regulating the rDNA promoters activity. Immunofluorescence analysis and biochemical fractionation showed that all three DNMTs (DNMT1, DNMT3A, and DNMT3B) are associated with the inactive rDNA in the nucleolus. Although DNMTs associate with both methylated and unmethylated rDNA promoters, DNMT1 preferentially associates with the methylated genes. The rDNA primary transcript level was significantly elevated in DNMT1-/- or DNMT3B-/- human colon carcinoma (HCT116) cells. Southern blot analysis demonstrated a moderate level of rDNA promoter hypomethylation in DNMT1-/- cells and a dramatic loss of rDNA promoter methylation in double knockout cells. Transient overexpression of DNMT1 or DNMT3B suppressed the luciferase expression from both methylated and unmethylated pHrD-IRES-Luc, a reporter plasmid where the rDNA promoter drives luciferase expression. DNMT1-mediated suppression of the unmethylated promoter involves de novo methylation of the promoter, whereas histone deacetylase 2 cooperates with DNMT1 to inhibit the methylated rDNA promoter. Unlike DNMT1, both the wild type and catalytically inactive DNMT3B mutant can suppress rDNA promoter irrespective of its methylation status. DNMT3B-mediated suppression of the rDNA promoter also involves histone deacetylation. Treatment of HCT116 cells with Decitabine (a DNMT inhibitor) or trichostatin A (a histone deacetylase inhibitor) up-regulated endogenous rDNA expression. These inhibitors synergistically activated methylated pHrD-IRES-Luc, whereas they exhibited additive effects on the unmethylated promoter. These results demonstrate localization of DNMTs with the inactive rDNA in the nucleolus, the specific role of DNMT1 and DNMT3B in rDNA expression and the differential regulation of rDNA expression from the methylated and unmethylated rDNA promoters.

Indexed as

Transcription, GeneticAnimalsCell LineDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNA MethylationDNA Methyltransferase 3ADNA Methyltransferase 3BDNA Modification MethylasesDNA, RibosomalGene Expression RegulationHumansMicePromoter Regions, GeneticRNA, RibosomalTransfectionDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADNA Methyltransferase 3BDNA Modification MethylasesDNA, RibosomalDNMT1 protein, humanDnmt1 protein, mouseDNMT3A protein, humanDnmt3a protein, mouseRNA, Ribosomal

Identifiers

PMID16735507
PMCPMC2243234
OpenAlexW2082225623

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.