Evidence map›Paper›PMID 10435592›Full record

ArticleOncogene1999

Site-specific DNA methylation in the neurofibromatosis (NF1) promoter interferes with binding of CREB and SP1 transcription factors.

D N Mancini, S M Singh, T K Archer, D I Rodenhiser

Abstract readComparative Study
PubMed Publisher
In one paragraph

Article in Oncogene, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
4.2field-weighted citation impact, top 6% 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

55 citing papers in PubMed, 130 citations in OpenAlex.

  1. Multi-faceted regulation of CREB family transcription factors.Frontiers in molecular neuroscience · 2024
    Review
  2. Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. What turns CREB on? And off? And why does it matter?Cellular and molecular life sciences : CMLS · 2020
    Review
  8. Article
  9. Article
  10. Article
  11. Association between Promoter Methylation of Gene ERCC3 and Benzene Hematotoxicity.International journal of environmental research and public health · 2017
    Article
  12. Article
  13. Review
  14. DNA methylation alterations in the pathogenesis of lupus.Clinical and experimental immunology · 2017
    Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. 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 3 institutions in 1 country.

D N ManciniMolecular Medical Genetics Program, Child Health Research Institute, London Health Sciences Centre, Department of Paediatrics, University of Western Ontario, Canada.
S M Singh
T K Archer
D I Rodenhiser
London Health Sciences Centre · CAChildren’s Health Research Institute · CAWestern University · CA

Funding

Transcriptional Functions of Nuclear Receptors in Cancer CellsZIAES071006 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI ARCHER, TREVOR KEITH · 2009 to 2025
$58.0M
Transcriptional Functions of Nuclear Receptors in Cancer CellsZ01ES071006 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI ARCHER, TREVOR KEITH · 1999 to 2008
$6.9M
Development Of New Hormone Responsive Models From CancerZ01ES071007 · NIEHS · ENVIRONMENTAL HEALTH SCIENCES · PI ARCHER, TREVOR K · 1999 to 2002
–
6 · The paper itself

Abstract

Tumour suppressor genes and growth regulatory genes are frequent targets for methylation defects that can result in aberrant expression and mutagenesis. We have established a methylation map of the promoter region of the neurofibromatosis (NF1) gene and demonstrated functional sensitivity for methylation at specific sites for the SP1 and CRE binding (CREB) proteins in the NF1 regulatory region. We evaluated the methylation status of CpG dinucleotides within five promoter subregions in the human and mouse homologues of the neurofibromatosis (NF1) genes. Three 5' subregions were found to be consistently methylated in all the tissues analysed. In contrast, DNA methylation was absent in the vicinity of the transcription start site bounded by SP1 recognition sequences. Gelshift assays showed that methylation specifically inhibits the CREB transcription factor from binding to its recognition site at the NF1 transcription start site. Furthermore, SP1 elements within the NF1 promoter are methylation sensitive, particularly when methylation is present on the antisense strand. We propose that for NF1 as with several other tumour suppressor genes, CpG methylation occurs in a complex, site-specific manner with the maintenance of a methylation-free promoter region bounded by SP1 binding sites that allow an accessible promoter to be retained. When these SP1 boundaries are breached, methylation can sweep in, rendering the promoter inaccessible for specific methylation-sensitive transcription factors and leading to a loss of functional integrity of the methylation-free CpG island.

Indexed as

CpG IslandsDNA MethylationGenes, Neurofibromatosis 1Promoter Regions, GeneticAnimalsBinding, CompetitiveBinding SitesCyclic AMP Response Element-Binding ProteinDNAGene Expression RegulationHumansMiceOrgan SpecificityPolymerase Chain ReactionProtein BindingSp1 Transcription FactorCyclic AMP Response Element-Binding ProteinDNASp1 Transcription Factor

Identifiers

PMID10435592
OpenAlexW2091529776

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.