This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lazorchak, A. S.
Right arrow Articles by Zhuang, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lazorchak, A. S.
Right arrow Articles by Zhuang, Y.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, February 2006, p. 810-821, Vol. 26, No. 3
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.3.810-821.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

E2A and IRF-4/Pip Promote Chromatin Modification and Transcription of the Immunoglobulin {kappa} Locus in Pre-B Cells

Adam S. Lazorchak,1 Mark S. Schlissel,2 and Yuan Zhuang1*

Department of Immunology, Duke University Medical Center, Box 3010, 328 Jones Building, Research Drive, Durham, North Carolina 27710,1 Department of Molecular and Cell Biology, University of California, 439 Life Sciences Addition, Berkeley, California 947202

Received 18 July 2005/ Returned for modification 15 September 2005/ Accepted 11 November 2005

The immunoglobulin kappa light chain (Ig{kappa}) 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 ({kappa}Ei) and the 3' enhancer ({kappa}E3'), flanking the constant exon. E2A transcription factors have been indicated to be directly involved in the regulation of Ig{kappa} locus activation. In this study, we utilize E2A-deficient pre-B cells to directly investigate the mechanism of E2A-mediated Ig{kappa} activation. We demonstrate that Ig{kappa} 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 Ig{kappa} and rescue Ig{kappa} germ line transcription and J{kappa} gene recombinase accessibility. Furthermore, we show that increased E2A recruitment to {kappa}Ei and {kappa}E3' correlates with activation of Ig{kappa} in pre-B cells and that recruitment of E2A to {kappa}E3' 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 Ig{kappa} germ line transcription and enhancer acetylation. In the absence of E2A, increased IRF-4 expression is not sufficient to promote Ig{kappa} enhancer chromatin modification or transcription, suggesting that the sequential involvement of IRF-4 and E2A is necessary for the activation of the Ig{kappa} 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 Ig{kappa} gene activation.

* Corresponding author. Mailing address: Department of Immunology, Duke University Medical Center, Box 3010, 328 Jones Building, Research Drive, Durham, NC 27710. Phone: (919) 613-7824. Fax: (919) 613-7853. E-mail: yzhuang{at}duke.edu.

Molecular and Cellular Biology, February 2006, p. 810-821, Vol. 26, No. 3
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.3.810-821.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Beck, K., Peak, M. M., Ota, T., Nemazee, D., Murre, C. (2009). Distinct roles for E12 and E47 in B cell specification and the sequential rearrangement of immunoglobulin light chain loci. JEM 206: 2271-2284 [Abstract] [Full Text]  
  • Liu, Z., Ma, Z., Terada, L. S., Garrard, W. T. (2009). Divergent Roles of RelA and c-Rel in Establishing Chromosomal Loops upon Activation of the Ig{kappa} Gene. J. Immunol. 183: 3819-3830 [Abstract] [Full Text]  
  • Yabuki, M., Ordinario, E. C., Cummings, W. J., Fujii, M. M., Maizels, N. (2009). E2A Acts in cis in G1 Phase of Cell Cycle to Promote Ig Gene Diversification. J. Immunol. 182: 408-415 [Abstract] [Full Text]  
  • Kikuchi, K., Kasai, H., Watanabe, A., Lai, A. Y., Kondo, M. (2008). IL-7 Specifies B Cell Fate at the Common Lymphoid Progenitor to Pre-ProB Transition Stage by Maintaining Early B Cell Factor Expression. J. Immunol. 181: 383-392 [Abstract] [Full Text]  
  • Pathak, S., Ma, S., Trinh, L., Lu, R. (2008). A Role for Interferon Regulatory Factor 4 in Receptor Editing. Mol. Cell. Biol. 28: 2815-2824 [Abstract] [Full Text]  
  • Dieterich, C., Franz, M. W., Vingron, M. (2007). Developments in CORG: a gene-centric comparative genomics resource. Nucleic Acids Res 35: D32-D35 [Abstract] [Full Text]  
  • Ma, S., Turetsky, A., Trinh, L., Lu, R. (2006). IFN Regulatory Factor 4 and 8 Promote Ig Light Chain {kappa} Locus Activation in Pre-B Cell Development. J. Immunol. 177: 7898-7904 [Abstract] [Full Text]  
  • Lazorchak, A. S., Wojciechowski, J., Dai, M., Zhuang, Y. (2006). E2A Promotes the Survival of Precursor and Mature B Lymphocytes. J. Immunol. 177: 2495-2504 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»