International Immunology, Vol. 13, No. 6, 733-746,
June 2001
© 2001 Japanese Society for Immunology
Roles of Ets proteins, NF-
B and nocodazole in regulating induction of transcription of mouse germline Ig 
RNA by transforming growth factor-ß1
Department of Molecular Genetics and Microbiology, Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, MA 01655-0122, USA
1 Department of Microbiology, College of Natural Sciences, Kangwon National University, Chunchon 200-701, Korea
Correspondence to: J. Stavnezer
Antibody class switch recombination (CSR) occurs after antigen activation of B cells. CSR is directed to specific heavy chain isotypes by cytokines and B cell activators that induce transcription from the unrearranged, or germline (GL), CH region genes. Transforming growth factor (TGF)-ß1 is essential for switch recombination to IgA due to its ability to induce transcription from GL Ig 
genes. It has been shown that the promoters which regulate transcription of mouse and human GL RNAs contain a TGF-ß1-responsive element that binds Smad and core binding factor (CBF)/AML/PEBP/Runx. They also contain other elements which bind the transcription factors CREB, BSAP and Ets family proteins. In this manuscript we demonstrate that two tandem Ets sites in the mouse GL promoter bind the transcription factors Elf-1 and PU.1, and that the 3' site is essential for expression of a luciferase reporter gene driven by the GL promoter. Binding of Elf-1 to the GL promoter is inducible by lipopolysaccharide in nuclear extracts from splenic B cells. An NF-
B site is identified, although it does not contribute to expression of the promoter in reporter gene assays. Since CSR to IgA is greatly reduced in NF-B/p50-deficient mice, these data support the hypothesis that NF-B has roles in switching in addition to regulation of GL transcription. Finally, we demonstrate that nocodazole, which disrupts microtubules that sequester Smad proteins in the cytoplasm, stimulates transcription from the GL promoter.
Keywords: antibody class switch, Elf-1, IgA
Transmitting editor: K. Knight
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Zhu, W. Wang, D. C. Clarke, and X. Liu Activation of Mps1 Promotes Transforming Growth Factor-beta-independent Smad Signaling J. Biol. Chem., June 22, 2007; 282(25): 18327 - 18338. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-C. Chen, J. C. Byrd, and N. Muthusamy Differential Role for Cyclic AMP Response Element Binding Protein-1 in Multiple Stages of B Cell Development, Differentiation, and Survival J. Immunol., February 15, 2006; 176(4): 2208 - 2218. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Takeshita, K. Suzuki, S. Sasaki, N. Ishii, D. M. Klinman, and K. J. Ishii Transcriptional Regulation of the Human TLR9 Gene J. Immunol., August 15, 2004; 173(4): 2552 - 2561. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Yang, L. Zhang, Y. Zhang, and H. H. Kazazian Jr An important role for RUNX3 in human L1 transcription and retrotransposition Nucleic Acids Res., August 15, 2003; 31(16): 4929 - 4940. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Austin, K. M. Haas, S. M. Naugler, A. A. Bajer, D. Garcia-Tapia, and D. M. Estes Identification and Characterization of a Novel Regulatory Factor: IgA-Inducing Protein J. Immunol., August 1, 2003; 171(3): 1336 - 1342. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. O'Reilly, C. M. Quinn, T. El-Shanawany, S. Gordon, and D. R. Greaves Multiple Ets Factors and Interferon Regulatory Factor-4 Modulate CD68 Expression in a Cell Type-specific Manner J. Biol. Chem., June 6, 2003; 278(24): 21909 - 21919. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Dennler, M.-J. Goumans, and P. ten Dijke Transforming growth factor {beta} signal transduction J. Leukoc. Biol., May 1, 2002; 71(5): 731 - 740. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Spieker-Polet, P.-C. Yam, and K. L. Knight Functional Analysis of I{alpha} Promoter Regions of Multiple IgA Heavy Chain Genes J. Immunol., April 1, 2002; 168(7): 3360 - 3368. [Abstract] [Full Text] [PDF]
|
|