Nucleic Acids Research, 2003, Vol. 31, No. 19 5483-5489
© 2003 Oxford University Press
Requirements for selective recruitment of Ets proteins and activation of mb-1/Ig-
gene transcription by Pax-5 (BSAP)
Integrated Department of Immunology, National Jewish Medical and Research Center and University of Colorado Health Sciences Center, Denver, CO 80262, USA, 1 Biochemistry and Molecular Biology, School of Biomedical and Chemical Sciences and Western Australia Institute for Medical Research, The University of Western Australia, Crawley 6009, Australia and 2 Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, Baltimore, MD 21250, USA
*To whom correspondence should be addressed. Tel: +1 303 398 1398; Fax: +1 303 398 1396; Email: hagmanj{at}njc.org
Pax-5, a member of the paired domain family of transcription factors, is a key regulator of B lymphocyte-specific transcription and differentiation. A major target of Pax-5-mediated activation is the mb-1 gene, which encodes the essential transmembrane signaling protein Ig-
. Pax-5 recruits three members of the Ets family of transcription factors: Ets-1, Fli-1 and GABP (with GABPß1), to assemble ternary complexes on the mb-1 promoter in vitro. Using the Pax-5:Ets-1:DNA crystal structure as a guide, we defined amino acid requirements for transcriptional activation of endogenous mb-1 genes using a novel cell-based assay. Mutations in the ß-hairpin/ß-turn of the DNA-binding domain of Pax-5 demonstrated its importance for DNA sequence recognition and activation of mb-1 transcription. Mutations of amino acids contacting Ets-1 in the crystal structure reduced or blocked mb-1 promoter activation. One of these mutations, Q22A, resulted in greatly reduced mb-1 gene transcript levels, concurrent with the loss of its ability to recruit Fli-1 to bind the promoter in vitro. In contrast, the mutation had no effect on recruitment of the related Ets protein GABP (with GABPß1). These data further define requirements for Pax-5 function in vivo and reveal the complexity of interactions required for cooperative partnerships between transcription factors.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C. G. Mullighan, X. Su, J. Zhang, I. Radtke, L. A.A. Phillips, C. B. Miller, J. Ma, W. Liu, C. Cheng, B. A. Schulman, et al. Deletion of IKZF1 and Prognosis in Acute Lymphoblastic Leukemia N. Engl. J. Med., January 29, 2009; 360(5): 470 - 480. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. K. Zhang, O. Moussa, A. LaRue, S. Bradshaw, I. Molano, D. D. Spyropoulos, G. S. Gilkeson, and D. K. Watson The Transcription Factor Fli-1 Modulates Marginal Zone and Follicular B Cell Development in Mice J. Immunol., August 1, 2008; 181(3): 1644 - 1654. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-H. Xue, X. Jing, J. Bollenbacher-Reilley, D.-M. Zhao, J. S. Haring, B. Yang, C. Liu, G. A. Bishop, J. T. Harty, and W. J. Leonard Targeting the GA Binding Protein {beta}1L Isoform Does Not Perturb Lymphocyte Development and Function Mol. Cell. Biol., July 1, 2008; 28(13): 4300 - 4309. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. John, J. L. Clements, L. M. Russell, and L. A. Garrett-Sinha Ets-1 Regulates Plasma Cell Differentiation by Interfering with the Activity of the Transcription Factor Blimp-1 J. Biol. Chem., January 11, 2008; 283(2): 951 - 962. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Fazio, C. Palmi, A. Rolink, A. Biondi, and G. Cazzaniga PAX5/TEL Acts as a Transcriptional Repressor Causing Down-modulation of CD19, Enhances Migration to CXCL12, and Confers Survival Advantage in pre-BI Cells Cancer Res., January 1, 2008; 68(1): 181 - 189. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. K. Zhang and D. K. Watson The FLI-1 Transcription Factor Is a Short-Lived Phosphoprotein in T Cells J. Biochem., March 1, 2005; 137(3): 297 - 302. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. K. Zhang, S. Gallant, I. Molano, O. M. Moussa, P. Ruiz, D. D. Spyropoulos, D. K. Watson, and G. Gilkeson Decreased Expression of the Ets Family Transcription Factor Fli-1 Markedly Prolongs Survival and Significantly Reduces Renal Disease in MRL/lpr Mice J. Immunol., November 15, 2004; 173(10): 6481 - 6489. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. C. Hollenhorst, D. A. Jones, and B. J. Graves Expression profiles frame the promoter specificity dilemma of the ETS family of transcription factors Nucleic Acids Res., October 21, 2004; 32(18): 5693 - 5702. [Abstract] [Full Text] [PDF]
|
|