GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com


Jump to: navigation, search

Lazorchak, AS, Schlissel, MS and Zhuang, Y (2006) E2A and IRF-4/Pip promote chromatin modification and transcription of the immunoglobulin kappa locus in pre-B cells. Mol. Cell. Biol. 26:810-21


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.


PubMed PMC1347029 Online version:10.1128/MCB.26.3.810-821.2006


Acetylation; Animals; B-Lymphocytes/cytology; B-Lymphocytes/immunology; B-Lymphocytes/metabolism; Basic Helix-Loop-Helix Transcription Factors/genetics; Basic Helix-Loop-Helix Transcription Factors/metabolism; Cell Differentiation; Chromatin/metabolism; Enhancer Elements, Genetic; Gene Dosage; Gene Rearrangement, B-Lymphocyte, Light Chain; Germ Cells/metabolism; Histones/metabolism; Humans; Immunoglobulin kappa-Chains/genetics; Interferon Regulatory Factors/antagonists & inhibitors; Interferon Regulatory Factors/metabolism; Mice; Mice, Mutant Strains; Mutation; Piperazines/pharmacology; Protein Kinase Inhibitors/pharmacology; Pyrimidines/pharmacology; Recombination, Genetic; Transcription, Genetic; Transcriptional Activation



Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status

See also


See Help:References for how to manage references in GONUTS.