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
Services
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 Nagulapalli, S.
Right arrow Articles by Atchison, M. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nagulapalli, S.
Right arrow Articles by Atchison, M. L.

 Previous Article  |  Next Article 

Mol Cell Biol, August 1998, p. 4639-4650, Vol. 18, No. 8
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Transcription Factor Pip Can Enhance DNA Binding by E47, Leading to Transcriptional Synergy Involving Multiple Protein Domains

Sujatha Nagulapalli and Michael L. Atchison*

Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6046

Received 26 November 1997/Returned for modification 7 January 1998/Accepted 11 May 1998

The transcription factors E2A (E12/E47) and Pip are both required for normal B-cell development. Each protein binds to regulatory sequences within various immunoglobulin enhancer elements. Activity of E2A proteins can be regulated by interactions with other proteins which influence their DNA binding or activation potential. Similarly, Pip function can be influenced by interaction with the protein PU.1, which can recruit Pip to bind to DNA. We show here that a previously unidentified Pip binding site resides adjacent to the E2A binding site within the immunoglobulin kappa  3' enhancer. Both of these binding sites are crucial for high-level enhancer activity. We found that E47 and Pip can functionally interact to generate a very potent 100-fold transcriptional synergy. Through a series of mutagenesis experiments, we identified the Pip sequences necessary for transcriptional activation and for synergy with E47. Two synergy domains (residues 140 to 207 and 300 to 420) in addition to the Pip DNA binding domain (residues 1 to 134) are required for maximal synergy with E47. We also identified a Pip domain (residues 207 to 300) that appears to mask Pip transactivation potential. Part of the synergy mechanism between E47 and Pip appears to involve the ability of Pip to increase DNA binding by E47, perhaps by inducing a conformational change in the E47 protein. E47 may also induce a conformational change in Pip which unmasks sequences important for transcriptional activity. Based upon our results, we propose a model for E47-Pip transcriptional synergy.

* Corresponding author. Mailing address: University of Pennsylvania, School of Veterinary Medicine, 3800 Spruce St., Philadelphia, PA 19104. Phone: (215) 898-6428. Fax: (215) 898-9923. E-mail: atchison{at}vet.upenn.edu.

Mol Cell Biol, August 1998, p. 4639-4650, Vol. 18, No. 8
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Wei, F., Zaprazna, K., Wang, J., Atchison, M. L. (2009). PU.1 Can Recruit BCL6 to DNA To Repress Gene Expression in Germinal Center B Cells. Mol. Cell. Biol. 29: 4612-4622 [Abstract] [Full Text]  
  • Shaffer, A. L., Emre, N.C. T., Romesser, P. B., Staudt, L. M. (2009). IRF4: Immunity. Malignancy! Therapy?. Clin. Cancer Res. 15: 2954-2961 [Abstract] [Full Text]  
  • Wang, H., Lee, C. H., Qi, C., Tailor, P., Feng, J., Abbasi, S., Atsumi, T., Morse, H. C. III (2008). IRF8 regulates B-cell lineage specification, commitment, and differentiation. Blood 112: 4028-4038 [Abstract] [Full Text]  
  • Honma, K., Kimura, D., Tominaga, N., Miyakoda, M., Matsuyama, T., Yui, K. (2008). Interferon regulatory factor 4 differentially regulates the production of Th2 cytokines in naive vs. effector/memory CD4+ T cells. Proc. Natl. Acad. Sci. USA 105: 15890-15895 [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]  
  • Ma, S., Pathak, S., Trinh, L., Lu, R. (2008). Interferon regulatory factors 4 and 8 induce the expression of Ikaros and Aiolos to down-regulate pre-B-cell receptor and promote cell-cycle withdrawal in pre-B-cell development. Blood 111: 1396-1403 [Abstract] [Full Text]  
  • Hauser, J., Sveshnikova, N., Wallenius, A., Baradaran, S., Saarikettu, J., Grundstrom, T. (2008). B-cell receptor activation inhibits AID expression through calmodulin inhibition of E-proteins. Proc. Natl. Acad. Sci. USA 105: 1267-1272 [Abstract] [Full Text]  
  • Yang, D., Thangaraju, M., Browning, D. D., Dong, Z., Korchin, B., Lev, D. C., Ganapathy, V., Liu, K. (2007). IFN Regulatory Factor 8 Mediates Apoptosis in Nonhemopoietic Tumor Cells via Regulation of Fas Expression. J. Immunol. 179: 4775-4782 [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]  
  • Hodawadekar, S., Wei, F., Yu, D., Thomas-Tikhonenko, A., Atchison, M. L. (2006). Epigenetic Histone Modifications Do Not Control Ig{kappa} Locus Contraction and Intranuclear Localization in Cells with Dual B Cell-Macrophage Potential. J. Immunol. 177: 6165-6171 [Abstract] [Full Text]  
  • Lazorchak, A. S., Schlissel, M. S., 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: 810-821 [Abstract] [Full Text]  
  • Lee, C. H., Melchers, M., Wang, H., Torrey, T. A., Slota, R., Qi, C.-F., Kim, J. Y., Lugar, P., Kong, H. J., Farrington, L., van der Zouwen, B., Zhou, J. X., Lougaris, V., Lipsky, P. E., Grammer, A. C., Morse, H. C. III (2006). Regulation of the germinal center gene program by interferon (IFN) regulatory factor 8/IFN consensus sequence-binding protein. JEM 203: 63-72 [Abstract] [Full Text]  
  • Yoshida, K., Yamamoto, K., Kohno, T., Hironaka, N., Yasui, K., Kojima, C., Mukae, H., Kadota, J.-i., Suzuki, S., Honma, K., Kohno, S., Matsuyama, T. (2005). Active repression of IFN regulatory factor-1-mediated transactivation by IFN regulatory factor-4. Int Immunol 17: 1463-1471 [Abstract] [Full Text]  
  • Bai, Y., Srinivasan, L., Perkins, L., Atchison, M. L. (2005). Protein Acetylation Regulates Both PU.1 Transactivation and Ig{kappa} 3' Enhancer Activity. J. Immunol. 175: 5160-5169 [Abstract] [Full Text]  
  • Hashmueli, S., Gleit-Kielmanowicz, M., Meraro, D., Azriel, A., Melamed, D., Levi, B.-Z. (2003). A truncated IFN-regulatory factor-8\IFN consensus sequence-binding protein acts as dominant-negative, interferes with endogenous protein-protein interactions and leads to apoptosis of immune cells. Int Immunol 15: 807-815 [Abstract] [Full Text]  
  • Gobin, S. J. P., Biesta, P., Van den Elsen, P. J. (2003). Regulation of human beta 2-microglobulin transactivation in hematopoietic cells. Blood 101: 3058-3064 [Abstract] [Full Text]  
  • Fanzo, J. C., Hu, C.-M., Jang, S. Y., Pernis, A. B. (2003). Regulation of Lymphocyte Apoptosis by Interferon Regulatory Factor 4 (IRF-4). JEM 197: 303-314 [Abstract] [Full Text]  
  • Nagulapalli, S., Goheer, A., Pitt, L., McIntosh, L. P., Atchison, M. L. (2002). Mechanism of E47-Pip Interaction on DNA Resulting in Transcriptional Synergy and Activation of Immunoglobulin Germ Line Sterile Transcripts. Mol. Cell. Biol. 22: 7337-7350 [Abstract] [Full Text]  
  • Meraro, D., Gleit-Kielmanowicz, M., Hauser, H., Levi, B.-Z. (2002). IFN-Stimulated Gene 15 Is Synergistically Activated Through Interactions Between the Myelocyte/Lymphocyte-Specific Transcription Factors, PU.1, IFN Regulatory Factor-8/IFN Consensus Sequence Binding Protein, and IFN Regulatory Factor-4: Characterization of a New Subtype of IFN-Stimulated Response Element. J. Immunol. 168: 6224-6231 [Abstract] [Full Text]  
  • Dai, Y.-S., Cserjesi, P. (2002). The Basic Helix-Loop-Helix Factor, HAND2, Functions as a Transcriptional Activator by Binding to E-boxes as a Heterodimer. J. Biol. Chem. 277: 12604-12612 [Abstract] [Full Text]  
  • Bose, H. R. Jr. (2001). Interferon Regulatory Factor 4 Contributes to Transformation of v-Rel-Expressing Fibroblasts. Mol. Cell. Biol. 21: 6369-6386 [Abstract] [Full Text]  
  • Sigvardsson, M. (2000). Overlapping Expression of Early B-Cell Factor and Basic Helix-Loop-Helix Proteins as a Mechanism To Dictate B-Lineage-Specific Activity of the lambda 5 Promoter. Mol. Cell. Biol. 20: 3640-3654 [Abstract] [Full Text]  
  • Gupta, S., Jiang, M., Anthony, A., Pernis, A. B. (1999). Lineage-Specific Modulation of Interleukin 4 Signaling by Interferon Regulatory Factor 4. JEM 190: 1837-1848 [Abstract] [Full Text]  
  • Meraro, D., Hashmueli, S., Koren, B., Azriel, A., Oumard, A., Kirchhoff, S., Hauser, H., Nagulapalli, S., Atchison, M. L., Levi, B.-Z. (1999). Protein-Protein and DNA-Protein Interactions Affect the Activity of Lymphoid-Specific IFN Regulatory Factors. J. Immunol. 163: 6468-6478 [Abstract] [Full Text]  
  • Marecki, S., Atchison, M. L., Fenton, M. J. (1999). Differential Expression and Distinct Functions of IFN Regulatory Factor 4 and IFN Consensus Sequence Binding Protein in Macrophages. J. Immunol. 163: 2713-2722 [Abstract] [Full Text]  
  • Cohen, H., Azriel, A., Cohen, T., Meraro, D., Hashmueli, S., Bech-Otschir, D., Kraft, R., Dubiel, W., Levi, B.-Z. (2000). Interaction between Interferon Consensus Sequence-binding Protein and COP9/Signalosome Subunit CSN2 (Trip15). A POSSIBLE LINK BETWEEN INTERFERON REGULATORY FACTOR SIGNALING AND THE COP9/SIGNALOSOME. J. Biol. Chem. 275: 39081-39089 [Abstract] [Full Text]  
  • Mullick, J., Anandatheerthavarada, H. K., Amuthan, G., Bhagwat, S. V., Biswas, G., Camasamudram, V., Bhat, N. K., Reddy, S. E. P., Rao, V., Avadhani, N. G. (2001). Physical Interaction and Functional Synergy between Glucocorticoid Receptor and Ets2 Proteins for Transcription Activation of the Rat Cytochrome P-450c27 Promoter. J. Biol. Chem. 276: 18007-18017 [Abstract] [Full Text]  
  • Rengarajan, J., Mowen, K. A., McBride, K. D., Smith, E. D., Singh, H., Glimcher, L. H. (2002). Interferon Regulatory Factor 4 (IRF4) Interacts with NFATc2 to Modulate Interleukin 4 Gene Expression. JEM 195: 1003-1012 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»