ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Ebf1 and c-Myb repress rag transcription downstream of Stat5 during early B cell development.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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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.
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Who cites it
13 citing papers in PubMed, 31 citations in OpenAlex.
- Article
- Article
- Early B-Cell Factor 1: An Archetype for a Lineage-Restricted Transcription Factor Linking Development to Disease.Advances in experimental medicine and biology · 2024Review
- EBF1, PAX5, and MYC: regulation on B cell development and association with hematologic neoplasms.Frontiers in immunology · 2024Review
- Transcription factor networks link B-lymphocyte development and malignant transformation in leukemia.Genes & development · 2023Review
- Non-Coding Variants in Cancer: Mechanistic Insights and Clinical Potential for Personalized Medicine.Non-coding RNA · 2021Review
- RAG deficiencies: Recent advances in disease pathogenesis and novel therapeutic approaches.European journal of immunology · 2021Review
- V(D)J recombination, somatic hypermutation and class switch recombination of immunoglobulins: mechanism and regulation.Immunology · 2020Review
- Control of Early B Cell Development by the RNA NCell reports · 2020Article
- A general computational approach to predicting synergistic transcriptional cores that determine cell subpopulation identities.Nucleic acids research · 2019Article
- Hierarchical assembly and disassembly of a transcriptionally active RAG locus in CD4The Journal of experimental medicine · 2019Article
- Dual Mechanism ofMolecular and cellular biology · 2017Article
- IL-7 coordinates proliferation, differentiation and Tcra recombination during thymocyte β-selection.Nature immunology · 2015Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
The temporal control of RAG (Rag) expression in developing lymphocytes prevents DNA breaks during periods of proliferation that could threaten genomic integrity. In developing B cells, the IL-7R and precursor B cell Ag receptor (pre-BCR) synergize to induce proliferation and the repression of Rag at the protein and mRNA levels for a brief period following successful Ig H chain gene rearrangement. Whereas the mechanism of RAG2 protein downregulation is well defined, little is known about the pathways and transcription factors that mediate transcriptional repression of Rag. Using Abelson murine leukemia virus-transformed B cells to model this stage of development, we identified early B cell factor 1 (Ebf1) as a strong repressor of Rag transcription. Short hairpin RNA-mediated knockdown of either Ebf1 or its downstream target c-Myb was sufficient to induce Rag transcription in these highly proliferative cells. Ebf1 and c-Myb antagonize Rag transcription by negatively regulating the binding of Foxo1 to the Rag locus. Ebf1 accomplishes this through both direct negative regulation of Foxo1 expression and direct positive regulation of Gfi1b expression. Ebf1 expression is driven by the IL-7R downstream effector Stat5, providing a link between the negative regulation of Rag transcription by IL-7 and a novel repressive pathway involving Ebf1 and c-Myb.
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Registered trials
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.