Evidence map›Paper›PMID 33619557›Full record

ArticleBlood2021

EBF1 and PAX5 control pro-B cell expansion via opposing regulation of the Myc gene.

Rajesh Somasundaram, Christina T Jensen, Johanna Tingvall-Gustafsson, Josefine Åhsberg, Kazuki Okuyama, Mahadesh Prasad, James R Hagman, Xun Wang, Shamit Soneji, Tobias Strid and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
6.3field-weighted citation impact, top 3% 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

31 citing papers in PubMed, 43 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. PAX Family, Master Regulator in Cancer.Diagnostics (Basel, Switzerland) · 2025
    Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. Article
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  20. Review
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

12 authors at 4 institutions in 2 countries.

Rajesh SomasundaramDepartment of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
Christina T JensenDivision of Molecular Hematology, Lund University, Lund, Sweden.ORCID 0000-0002-6753-7983
Johanna Tingvall-GustafssonDivision of Molecular Hematology, Lund University, Lund, Sweden.ORCID 0000-0002-7359-6584
Josefine ÅhsbergDepartment of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
Kazuki OkuyamaDepartment of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
Mahadesh PrasadDepartment of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
James R HagmanDepartment of Immunology and Genomic Medicine, National Jewish Health, Denver, CO.ORCID 0000-0002-5436-8455
Xun WangDivision of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA.ORCID 0000-0002-1653-5750
Shamit SonejiDivision of Molecular Hematology, Lund University, Lund, Sweden.
Tobias StridDepartment of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.ORCID 0000-0002-2166-5170
Jonas UngerbäckDivision of Molecular Hematology, Lund University, Lund, Sweden.ORCID 0000-0002-2190-3896
Mikael SigvardssonDepartment of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.ORCID 0000-0001-8527-7276
Linköping University · SELund University · SECalifornia Institute of Technology · USNational Jewish Health · US

Funding

Regulation of V(D)J Recombination by Arginine MethylationR21AI115696 · NIAID · NATIONAL JEWISH HEALTH · PI HAGMAN, JAMES R. · 2015 to 2016
$436k
NIAID NIH HHS R21 AI115696
6 · The paper itself

Abstract

Genes encoding B lineage-restricted transcription factors are frequently mutated in B-lymphoid leukemias, suggesting a close link between normal and malignant B-cell development. One of these transcription factors is early B-cell factor 1 (EBF1), a protein of critical importance for lineage specification and survival of B-lymphoid progenitors. Here, we report that impaired EBF1 function in mouse B-cell progenitors results in reduced expression of Myc. Ectopic expression of MYC partially rescued B-cell expansion in the absence of EBF1 both in vivo and in vitro. Using chromosome conformation analysis in combination with ATAC-sequencing, chromatin immunoprecipitation-sequencing, and reporter gene assays, six EBF1-responsive enhancer elements were identified within the Myc locus. CRISPR-Cas9-mediated targeting of EBF1-binding sites identified one element of key importance for Myc expression and pro-B cell expansion. These data provide evidence that Myc is a direct target of EBF1. Furthermore, chromatin immunoprecipitation-sequencing analysis revealed that several regulatory elements in the Myc locus are targets of PAX5. However, ectopic expression of PAX5 in EBF1-deficient cells inhibits the cell cycle and reduces Myc expression, suggesting that EBF1 and PAX5 act in an opposing manner to regulate Myc levels. This hypothesis is further substantiated by the finding that Pax5 inactivation reduces requirements for EBF1 in pro-B-cell expansion. The binding of EBF1 and PAX5 to regulatory elements in the human MYC gene in a B-cell acute lymphoblastic leukemia cell line indicates that the EBF1:PAX5:MYC regulatory loop is conserved and may control both normal and malignant B-cell development.

Indexed as

Gene Expression Regulation, LeukemicAnimalsCell ProliferationMiceMice, KnockoutPAX5 Transcription FactorPrecursor B-Cell Lymphoblastic Leukemia-LymphomaPrecursor Cells, B-LymphoidProto-Oncogene Proteins c-mycResponse ElementsTrans-ActivatorsEbf1 protein, mouseMYC protein, humanPax5 protein, mousePAX5 Transcription FactorProto-Oncogene Proteins c-mycTrans-Activators

Identifiers

PMID33619557
PMCPMC8176764
OpenAlexW3133173575

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.