ArticleThe Journal of experimental medicine2012
Gfi1b negatively regulates Rag expression directly and via the repression of FoxO1.
Article in The Journal of experimental medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 39 citations in OpenAlex.
- The Function of E2A in B-Cell Development.Advances in experimental medicine and biology · 2024Review
- The E-Id Axis Instructs Adaptive Versus Innate Lineage Cell Fate Choice and Instructs Regulatory T Cell Differentiation.Frontiers in immunology · 2022Review
- RAG deficiencies: Recent advances in disease pathogenesis and novel therapeutic approaches.European journal of immunology · 2021Review
- The Interplay Between Chromatin Architecture and Lineage-Specific Transcription Factors and the Regulation ofFrontiers in immunology · 2021Review
- Multifaceted Actions of GFI1 and GFI1B in Hematopoietic Stem Cell Self-Renewal and Lineage Commitment.Frontiers in genetics · 2020Review
- Hierarchical assembly and disassembly of a transcriptionally active RAG locus in CD4The Journal of experimental medicine · 2019Article
- Role of GFI1 in Epigenetic Regulation of MDS and AML Pathogenesis: Mechanisms and Therapeutic Implications.Frontiers in oncology · 2019Review
- Gfi1b: a key player in the genesis and maintenance of acute myeloid leukemia and myelodysplastic syndrome.Haematologica · 2018Article
- Dual Mechanism ofMolecular and cellular biology · 2017Article
- Multifunctional role of the transcription factor Blimp-1 in coordinating plasma cell differentiation.Nature immunology · 2016Article
- Cooperative Stimulation of Megakaryocytic Differentiation by Gfi1b Gene Targets Kindlin3 and Talin1.PloS one · 2016Article
- Reciprocal regulation of alternative lineages by Rgs18 and its transcriptional repressor Gfi1b.Journal of cell science · 2016Article
- Review
- CDK4 deficiency promotes genomic instability and enhances Myc-driven lymphomagenesis.The Journal of clinical investigation · 2014Article
- Article
- GFI1B, EVI5, MYB--additional genes that cooperate with the human BCL6 gene to promote the development of lymphomas.Blood cells, molecules & diseases · 2014Article
- Ebf1 and c-Myb repress rag transcription downstream of Stat5 during early B cell development.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- MK5 activates Rag transcription via Foxo1 in developing B cells.The Journal of experimental medicine · 2013Article
- Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Precise regulation of Rag (recombination-activating gene) expression is crucial to prevent genomic instability caused by the generation of Rag-mediated DNA breaks. Although mechanisms of Rag activation have been well characterized, the mechanism by which Rag expression is down-regulated in early B cell development has not been fully elucidated. Using a complementary DNA library screen, we identified the transcriptional repressor Gfi1b as negative regulator of the Rag locus. Expression of Gfi1b causes repression of Rag1 and Rag2 in cell lines and primary mouse cells. Conversely, Gfi1b-deficient cell lines exhibit increased Rag expression, double-strand breaks and recombination, and cell cycle defects. In primary cells, transcription of Gfi1b inversely correlates with Rag transcription, and simultaneous inactivation of Gfi1 and Gfi1b leads to an increase in Rag transcription early in B cell development. In addition, deletion of Gfi1 and Gfi1b in vivo results in a severe block in B cell development. Gfi1b orchestrates Rag repression via a dual mechanism. Direct binding of Gfi1b to a site 5' of the B cell-specific Erag enhancer results in epigenetic changes in the Rag locus, whereas indirect inhibition is achieved through repression of the trans-activator Foxo1. Together, our experiments show that Gfi family members are essential for normal B cell development and play an important role in modulating expression of the V(D)J recombinase.
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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.