Evidence map›Paper›PMID 9391093›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America1997

Methylation of the minimal promoter of an embryonic globin gene silences transcription in primary erythroid cells.

R Singal, R Ferris, J A Little, S Z Wang, G D Ginder

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

22 citing papers in PubMed, 88 citations in OpenAlex.

  1. Review
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  7. Advances in the understanding of haemoglobin switching.British journal of haematology · 2010
    Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Methyl binding domain protein 2 mediates gamma-globin gene silencing in adult human betaYAC transgenic mice.Proceedings of the National Academy of Sciences of the United States of America · 2006
    Article
  14. Article
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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

5 authors at 1 institution in 1 country.

R SingalDepartment of Medicine, Division of Medical Oncology, University of Minnesota, Minneapolis, MN 55455-0362, USA.
R Ferris
J A Little
S Z Wang
G D Ginder
University of Minnesota Medical Center · US

Funding

GLOBIN GENE REGULATION DURING ERYTHROID DIFFERENTIATIONR37DK029902 · NIDDK · VIRGINIA COMMONWEALTH UNIVERSITY · PI GINDER, GORDON D · 1992 to 1999
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NIDDK NIH HHS R37 DK029902NIDDK NIH HHS R-37DK29902
6 · The paper itself

Abstract

Methylation of cytosines in the dinucleotide CpG has been shown to suppress transcription of a number of tissue-specific genes, yet the precise mechanism is not fully understood. The vertebrate globin genes were among the first examples in which an inverse correlation was shown between CpG methylation and transcription. We studied the methylation pattern of the 235-bp rho-globin gene promoter in genomic DNA from primary chicken erythroid cells using the sodium bisulfite conversion technique and found all CpGs in the promoter to be methylated in erythroid cells from adult chickens in which the rho-globin gene is silent but unmethylated in 5-day (primitive) embryonic red cells in which the gene is transcribed. To elucidate further the mechanism of methylation-induced silencing, an expression construct consisting of 235 bp of 5' promoter sequence of the rho-globin gene along with a strong 5' erythroid enhancer driving a chloramphenicol acetyltransferase reporter gene, rho-CAT, was transfected into primary avian erythroid cells derived from 5-day embryos. Methylation of just the 235-bp rho-globin gene promoter fragment at every CpG resulted in a 20- to 30-fold inhibition of transcription, and this effect was not overridden by the presence of potent erythroid-specific enhancers. The ability of the 235-bp rho-globin gene promoter to bind to a DNA Methyl Cytosine binding Protein Complex (MeCPC) was tested in electrophoretic mobility shift assays utilizing primary avian erythroid cell nuclear extract. The results were that fully methylated but not unmethylated 235-bp rho-globin gene promoter fragment could compete efficiently for MeCPC binding. These results are a direct demonstration that site-specific methylation of a globin gene promoter at the exact CpGs that are methylated in vivo can silence transcription in homologous primary erythroid cells. Further, these data implicate binding of MeCPC to the promoter in the mechanism of silencing.

Indexed as

DNA MethylationPromoter Regions, GeneticAnimalsBase SequenceChick EmbryoChickensChloramphenicol O-AcetyltransferaseCpG IslandsDNADNA-Binding ProteinsDNA PrimersErythrocytesGenes, ReporterGlobinsHeLa CellsHumansChloramphenicol O-AcetyltransferaseDNADNA-Binding ProteinsDNA PrimersGlobins

Identifiers

PMID9391093
PMCPMC28373
OpenAlexW2076619054

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.