Evidence map›Paper›PMID 12612069›Full record

ArticleMolecular and cellular biology2003

Activation of the early B-cell-specific mb-1 (Ig-alpha) gene by Pax-5 is dependent on an unmethylated Ets binding site.

Holly Maier, Jeff Colbert, Daniel Fitzsimmons, Dawn R Clark, James Hagman

Open access · greenAbstract read
In one paragraph

Article in Molecular and cellular biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
2.1field-weighted citation impact, top 14% 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

43 citing papers in PubMed, 90 citations in OpenAlex.

  1. Review
  2. Epigenetic silencing of selected hypothalamic neuropeptides in narcolepsy with cataplexy.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  3. The Pleiotropy ofInternational journal of molecular sciences · 2022
    Review
  4. Review
  5. Review
  6. Hypoxia enhances CD8The Journal of allergy and clinical immunology · 2019
    Article
  7. Article
  8. Article
  9. Review
  10. Tissue-specific DNA demethylation is required for proper B-cell differentiation and function.Proceedings of the National Academy of Sciences of the United States of America · 2016
    Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Review
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  17. Review
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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.

Holly MaierIntegrated Department of Immunology, National Jewish Medical and Research Center, 1400 Jackson Street, K516B, Denver, CO 80206, USA.
Jeff Colbert
Daniel Fitzsimmons
Dawn R Clark
James Hagman
National Jewish Health · US

Funding

THE REGULATION OF V ALPHA 7 EXPRESSING T CELLSP01AI022295 · NIAID · NATIONAL JEWISH HEALTH · PI REFAELI, YOSEF · 1985 to 2011
$11.7M
TRAINING PROGRAM IN IMMUNOLOGYT32AI007405 · NIAID · UNIVERSITY OF COLORADO DENVER · PI Laurel L Lenz, Raul Martin Torres · 1991 to 2026
$10.5M
REGULATION OF B CELL DIFFERENTIATION IN VITROR01AI037574 · NIAID · NATIONAL JEWISH HEALTH · PI HAGMAN, JAMES R · 1997 to 2001
$547k
NIAID NIH HHS P01 AI022295NIAID NIH HHS P01 AI 22295NIAID NIH HHS R01 AI 37574NIAID NIH HHS T32 AI007405NIAID NIH HHS T32 AI 07405
6 · The paper itself

Abstract

Methylation of cytosine in CpG dinucleotides promotes transcriptional repression in mammals by blocking transcription factor binding and recruiting methyl-binding proteins that initiate chromatin remodeling. Here, we use a novel cell-based system to show that retrovirally expressed Pax-5 protein activates endogenous early B-cell-specific mb-1 genes in plasmacytoma cells, but only when the promoter is hypomethylated. CpG methylation does not directly affect binding of the promoter by Pax-5. Instead, methylation of an adjacent CpG interferes with assembly of ternary complexes comprising Pax-5 and Ets proteins. In electrophoretic mobility shift assays, recruitment of Ets-1 is blocked by methylation of the Ets site (5'CCGGAG) on the antisense strand. In transfection assays, selective methylation of a single CpG within the Pax-5-dependent Ets site greatly reduces mb-1 promoter activity. Prior demethylation of the endogenous mb-1 promoter is required for its activation by Pax-5 in transduced cells. Although B-lineage cells have only unmethylated mb-1 genes and do not modulate methylation of the mb-1 promoter during development, other tissues feature high percentages of methylated alleles. Together, these studies demonstrate a novel DNA methylation-dependent mechanism for regulating transcriptional activity through the inhibition of DNA-dependent protein-protein interactions.

Indexed as

AnimalsAntigens, CDBinding SitesB-LymphocytesBone Marrow CellsCD79 AntigensCell LineageCpG IslandsDNA-Binding ProteinsDNA MethylationGene Expression Regulation, NeoplasticHumansMacromolecular SubstancesMiceMice, Inbred BALB CMice, Inbred C57BLAntigens, CDCD79 AntigensCD79A protein, humanCd79a protein, mouseDNA-Binding ProteinsETS1 protein, humanEts1 protein, mouseMacromolecular SubstancesPAX5 protein, humanPax5 protein, mousePAX5 Transcription FactorProto-Oncogene Protein c-ets-1Proto-Oncogene ProteinsProto-Oncogene Proteins c-etsReceptors, Antigen, B-CellRecombinant Fusion ProteinsTranscription Factors

Identifiers

PMID12612069
PMCPMC149480
OpenAlexW2055766883

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.