ArticleMolecular and cellular biology2006
E2A and IRF-4/Pip promote chromatin modification and transcription of the immunoglobulin kappa locus in pre-B cells.
Article in Molecular and cellular biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 66 citations in OpenAlex.
- Article
- Temporal analyses reveal a pivotal role for sense and antisense enhancer RNAs in coordinate immunoglobulin lambda locus activation.Nucleic acids research · 2023Article
- A p38α-BLIMP1 signalling pathway is essential for plasma cell differentiation.Nature communications · 2022Article
- Helix-Loop-Helix Proteins in Adaptive Immune Development.Frontiers in immunology · 2022Review
- It Takes Three Receptors to Raise a B Cell.Trends in immunology · 2020Review
- Enhancers as regulators of antigen receptor loci three-dimensional chromatin structure.Transcription · 2020Review
- The miR-15 family reinforces the transition from proliferation to differentiation in pre-B cells.EMBO reports · 2017Article
- Local Chromatin Features Including PU.1 and IKAROS Binding and H3K4 Methylation Shape the Repertoire of Immunoglobulin Kappa Genes Chosen for V(D)J Recombination.Frontiers in immunology · 2017Article
- The interferon regulatory factors as novel potential targets in the treatment of cardiovascular diseases.British journal of pharmacology · 2015Review
- Orchestrating B cell lymphopoiesis through interplay of IL-7 receptor and pre-B cell receptor signalling.Nature reviews. Immunology · 2014Review
- Pre-B cell receptor signaling induces immunoglobulin κ locus accessibility by functional redistribution of enhancer-mediated chromatin interactions.PLoS biology · 2014Article
- A novel pax5-binding regulatory element in the igκ locus.Frontiers in immunology · 2014Article
- E proteins in lymphocyte development and lymphoid diseases.Current topics in developmental biology · 2014Review
- Extensive cooperation of immune master regulators IRF3 and NFκB in RNA Pol II recruitment and pause release in human innate antiviral transcription.Cell reports · 2013Article
- Epigenetic aspects of lymphocyte antigen receptor gene rearrangement or 'when stochasticity completes randomness'.Immunology · 2013Review
- Transcription factor Ebf1 regulates differentiation stage-specific signaling, proliferation, and survival of B cells.Genes & development · 2012Article
- A developmentally controlled competitive STAT5-PU.1 DNA binding mechanism regulates activity of the Ig κ E3' enhancer.Journal of immunology (Baltimore, Md. : 1950) · 2012Article
- Extensive gene-specific translational reprogramming in a model of B cell differentiation and Abl-dependent transformation.PloS one · 2012Article
- Epigenetic repression of the Igk locus by STAT5-mediated recruitment of the histone methyltransferase Ezh2.Nature immunology · 2011Article
- Forced expression of cyclin-dependent kinase 6 confers resistance of pro-B acute lymphocytic leukemia to Gleevec treatment.Molecular and cellular biology · 2011Article
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3 authors at 3 institutions in 1 country.
Funding
Abstract
The immunoglobulin kappa light chain (Igkappa) locus is regulated in a lineage- and stage-specific manner during B-cell development. The highly restricted timing of V to J gene recombination at the pre-B-cell stage is under the control of two enhancers, the intronic enhancer (kappaEi) and the 3' enhancer (kappaE3'), flanking the constant exon. E2A transcription factors have been indicated to be directly involved in the regulation of Igkappa locus activation. In this study, we utilize E2A-deficient pre-B cells to directly investigate the mechanism of E2A-mediated Igkappa activation. We demonstrate that Igkappa germ line transcription is severely impaired and recombination is blocked in the absence of E2A. Reconstitution of E2A-/- pre-B cells with inducible human E2A (E47R) is sufficient to promote chromatin modification of Igkappa and rescue Igkappa germ line transcription and Jkappa gene recombinase accessibility. Furthermore, we show that increased E2A recruitment to kappaEi and kappaE3' correlates with activation of Igkappa in pre-B cells and that recruitment of E2A to kappaE3' is in part dependent on the transcription factor IRF-4. Inhibition of IRF-4 expression in pre-B cells leads to a significant reduction of Igkappa germ line transcription and enhancer acetylation. In the absence of E2A, increased IRF-4 expression is not sufficient to promote Igkappa enhancer chromatin modification or transcription, suggesting that the sequential involvement of IRF-4 and E2A is necessary for the activation of the Igkappa locus. Finally, we provide genetic evidence in the mouse that E2A gene dosage can influence the development of pre-B cells during the phase of Igkappa gene activation.
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