This Article
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 Ernst, P.
Right arrow Articles by Smale, S. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ernst, P.
Right arrow Articles by Smale, S. T.

 Previous Article  |  Next Article 

Mol. Cell. Biol., 11 1996, 6121-6131, Vol 16, No. 11
Copyright © 1996, American Society for Microbiology

A potential role for Elf-1 in terminal transferase gene regulation

P Ernst, K Hahm, L Trinh, JN Davis, MF Roussel, CW Turck and ST Smale
Department of Microbiology and Immunology, UCLA School of Medicine, Los Angeles, California 90095-1662, USA.

The terminal deoxynucleotidyltransferase (TdT) gene represents an attractive model for the analysis of gene regulation during an early phase of lymphocyte development. In previous studies, we identified a DNA element, termed D', which is essential for TdT promoter activity in immature lymphocytes, and two classes of D'-binding factors, Ikaros proteins and Ets proteins. Here, we report a detailed mutant analysis of the D' element which suggests that an Ets protein, rather than an Ikaros protein, activates TdT transcription. Since multiple Ets proteins are expressed in developing lymphocytes and are capable of binding to the D' element, DNA affinity chromatography was used to determine if one of the Ets proteins might bind to the D' element with a uniquely high affinity, thereby implicating that protein as a potential TdT activator. Indeed, one binding activity was greatly enriched in the high-salt eluates from a D' affinity column. Peptide microsequencing revealed that the enriched protein was Elf-1. Immunoblot analyses confirmed that in nuclear extracts, Elf-1 has a significantly higher affinity for the D' sequence than does another Ets protein, Ets-1. Transactivation and expression studies support the hypothesis that Elf-1 activates TdT transcription in immature T and B cells. Finally, a D' mutation which selectively reduces Elf-1 binding, but not the binding of other Ets proteins, was found to greatly reduce TdT promoter activity. Although Elf-1 previously had been implicated in the inducible activation of genes in mature T and B cells, our results suggest that it also plays an important role in regulating genes during an early phase of lymphocyte development.


This article has been cited by other articles:

  • Gurel, Z., Ronni, T., Ho, S., Kuchar, J., Payne, K. J., Turk, C. W., Dovat, S. (2008). Recruitment of Ikaros to Pericentromeric Heterochromatin Is Regulated by Phosphorylation. J. Biol. Chem. 283: 8291-8300 [Abstract] [Full Text]  
  • Muller, F., Demeny, M. A., Tora, L. (2007). New Problems in RNA Polymerase II Transcription Initiation: Matching the Diversity of Core Promoters with a Variety of Promoter Recognition Factors. J. Biol. Chem. 282: 14685-14689 [Full Text]  
  • Smale, S. T. (2001). Core promoters: active contributors to combinatorial gene regulation. Genes Dev. 15: 2503-2508 [Full Text]  
  • Ortiz, B. D., Harrow, F., Cado, D., Santoso, B., Winoto, A. (2001). Function and Factor Interactions of a Locus Control Region Element in the Mouse T Cell Receptor-{alpha}/Dad1 Gene Locus. J. Immunol. 167: 3836-3845 [Abstract] [Full Text]  
  • Trinh, L. A., Ferrini, R., Cobb, B. S., Weinmann, A. S., Hahm, K., Ernst, P., Garraway, I. P., Merkenschlager, M., Smale, S. T. (2001). Down-regulation of TDT transcription in CD4+CD8+ thymocytes by Ikaros proteins in direct competition with an Ets activator. Genes Dev. 15: 1817-1832 [Abstract] [Full Text]  
  • Ernst, P., Wang, J., Huang, M., Goodman, R. H., Korsmeyer, S. J. (2001). MLL and CREB Bind Cooperatively to the Nuclear Coactivator CREB-Binding Protein. Mol. Cell. Biol. 21: 2249-2258 [Abstract] [Full Text]  
  • O'Neill, D. W., Schoetz, S. S., Lopez, R. A., Castle, M., Rabinowitz, L., Shor, E., Krawchuk, D., Goll, M. G., Renz, M., Seelig, H.-P., Han, S., Seong, R. H., Park, S. D., Agalioti, T., Munshi, N., Thanos, D., Erdjument-Bromage, H., Tempst, P., Bank, A. (2000). An Ikaros-Containing Chromatin-Remodeling Complex in Adult-Type Erythroid Cells. Mol. Cell. Biol. 20: 7572-7582 [Abstract] [Full Text]  
  • Dube, A., Akbarali, Y., Sato, T. N., Libermann, T. A., Oettgen, P. (1999). Role of the Ets Transcription Factors in the Regulation of the Vascular-Specific Tie2 Gene. Circ. Res. 84: 1177-1185 [Abstract] [Full Text]  
  • Rusterholz, C., Henrioud, P. C., Nabholz, M. (1999). Interleukin-2 (IL-2) Regulates the Accessibility of the IL-2-Responsive Enhancer in the IL-2 Receptor alpha  Gene to Transcription Factors. Mol. Cell. Biol. 19: 2681-2689 [Abstract] [Full Text]  
  • Karantzoulis-Fegaras, F., Antoniou, H., Lai, S.-L. M., Kulkarni, G., D'Abreo, C., Wong, G. K. T., Miller, T. L., Chan, Y., Atkins, J., Wang, Y., Marsden, P. A. (1999). Characterization of the Human Endothelial Nitric-oxide Synthase Promoter. J. Biol. Chem. 274: 3076-3093 [Abstract] [Full Text]  
  • Anderson, M., Hernandez-Hoyos, G, Diamond, R., Rothenberg, E. (1999). Precise developmental regulation of Ets family transcription factors during specification and commitment to the T cell lineage. Development 126: 3131-3148 [Abstract]  
  • ERNST, P., HAHM, K., COBB, B. S., BROWN, K. E., TRINH, L.A., MCCARTY, A.S., MERKENSCHLAGER, M., KLUG, C.A., FISHER, A.G., SMALE, S.T. (1999). Mechanisms of Transcriptional Regulation in Lymphocyte Progenitors: Insight from an Analysis of the Terminal Transferase Promoter. Cold Spring Harb Symp Quant Biol 64: 87-98 [Abstract]  
  • Bockamp, E.-O., Fordham, J. L., Gottgens, B., Murrell, A. M., Sanchez, M.-J., Green, A. R. (1998). Transcriptional Regulation of the Stem Cell Leukemia Gene by PU.1 and Elf-1. J. Biol. Chem. 273: 29032-29042 [Abstract] [Full Text]  
  • Hahm, K., Cobb, B. S., McCarty, A. S., Brown, K. E., Klug, C. A., Lee, R., Akashi, K., Weissman, I. L., Fisher, A. G., Smale, S. T. (1998). Helios, a T cell-restricted Ikaros family member that quantitatively associates with Ikaros at centromeric heterochromatin. Genes Dev. 12: 782-796 [Abstract] [Full Text]  
  • Rellahan, B. L., Jensen, J. P., Howcroft, T. K., Singer, D. S., Bonvini, E., Weissman, A. M. (1998). Elf-1 Regulates Basal Expression from the T Cell Antigen Receptor {zeta}-Chain Gene Promoter. J. Immunol. 160: 2794-2801 [Abstract] [Full Text]  
  • Klug, C. A., Morrison, S. J., Masek, M., Hahm, K., Smale, S. T., Weissman, I. L. (1998). Hematopoietic stem cells and lymphoid progenitors express different Ikaros isoforms, and Ikaros is localized to heterochromatin in immature lymphocytes. Proc. Natl. Acad. Sci. USA 95: 657-662 [Abstract] [Full Text]  
  • Serdobova, I., Pla, M., Reichenbach, P., Sperisen, P., Ghysdael, J., Wilson, A., Freeman, J., Nabholz, M. (1997). Elf-1 Contributes to the Function of the Complex Interleukin (IL)-2-responsive Enhancer in the Mouse IL-2 Receptor {alpha} Gene. JEM 185: 1211-1222 [Abstract] [Full Text]  
  • Mora-Garcia, P., Sakamoto, K. M. (2000). Granulocyte Colony-stimulating Factor Induces egr-1 Up-regulation through Interaction of Serum Response Element-binding Proteins. J. Biol. Chem. 275: 22418-22426 [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»