Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 29 September 1995:
Vol. 269. no. 5232, pp. 1866 - 1869
DOI: 10.1126/science.7569926

Articles

Science, Vol 269, Issue 5232, 1866-1869
Copyright © 1995 by American Association for the Advancement of Science


articles

Modulation of transcription factor Ets-1 DNA binding: DNA-induced unfolding of an alpha helix

JM Petersen, JJ Skalicky, LW Donaldson, LP McIntosh, T Alber, and BJ Graves

Department of Oncological Sciences, University of Utah School of Medicine, Salt Lake City 84132, USA.

Conformational changes, including local protein folding, play important roles in protein-DNA interactions. Here, studies of the transcription factor Ets-1 provided evidence that local protein unfolding also can accompany DNA binding. Circular dichroism and partial proteolysis showed that the secondary structure of the Ets-1 DNA-binding domain is unchanged in the presence of DNA. In contrast, DNA allosterically induced the unfolding of an alpha helix that lies within a flanking region involved in the negative regulation of DNA binding. These findings suggest a structural basis for the intramolecular inhibition of DNA binding and a mechanism for the cooperative partnerships that are common features of many eukaryotic transcription factors.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Ets-1 and Runx2 Regulate Transcription of a Metastatic Gene, Osteopontin, in Murine Colorectal Cancer Cells.
P. Y. Wai, Z. Mi, C. Gao, H. Guo, C. Marroquin, and P. C. Kuo (2006)
J. Biol. Chem. 281, 18973-18982
   Abstract »    Full Text »    PDF »
Variable Control of Ets-1 DNA Binding by Multiple Phosphates in an Unstructured Region.
M. A. Pufall, G. M. Lee, M. L. Nelson, H.-S. Kang, A. Velyvis, L. E. Kay, L. P. McIntosh, and B. J. Graves (2005)
Science 309, 142-145
   Abstract »    Full Text »    PDF »
The Structural and Dynamic Basis of Ets-1 DNA Binding Autoinhibition.
G. M. Lee, L. W. Donaldson, M. A. Pufall, H.-S. Kang, I. Pot, B. J. Graves, and L. P. McIntosh (2005)
J. Biol. Chem. 280, 7088-7099
   Abstract »    Full Text »    PDF »
The Transcriptional Repressor Nkx6.1 Also Functions as a Deoxyribonucleic Acid Context-Dependent Transcriptional Activator during Pancreatic {beta}-Cell Differentiation: Evidence for Feedback Activation of the nkx6.1 Gene by Nkx6.1.
T. Iype, D. G. Taylor, S. M. Ziesmann, J. C. Garmey, H. Watada, and R. G. Mirmira (2004)
Mol. Endocrinol. 18, 1363-1375
   Abstract »    Full Text »    PDF »
Combinatorial Control of DNase I-hypersensitive Site Formation and Erasure by Immunoglobulin Heavy Chain Enhancer-binding Proteins.
H. Ishii, R. Sen, and M. J. Pazin (2004)
J. Biol. Chem. 279, 7331-7338
   Abstract »    Full Text »    PDF »
Identification of Novel Domains within Sox-2 and Sox-11 Involved in Autoinhibition of DNA Binding and Partnership Specificity.
M. S. Wiebe, T. K. Nowling, and A. Rizzino (2003)
J. Biol. Chem. 278, 17901-17911
   Abstract »    Full Text »    PDF »
Cooperative Interaction of Hypoxia-inducible Factor-2alpha (HIF-2alpha ) and Ets-1 in the Transcriptional Activation of Vascular Endothelial Growth Factor Receptor-2 (Flk-1).
G. Elvert, A. Kappel, R. Heidenreich, U. Englmeier, S. Lanz, T. Acker, M. Rauter, K. Plate, M. Sieweke, G. Breier, et al. (2003)
J. Biol. Chem. 278, 7520-7530
   Abstract »    Full Text »    PDF »
Structural Analysis of the Autoinhibition of Ets-1 and Its Role in Protein Partnerships.
C. W. Garvie, M. A. Pufall, B. J. Graves, and C. Wolberger (2002)
J. Biol. Chem. 277, 45529-45536
   Abstract »    Full Text »    PDF »
Sp100 Interacts with ETS-1 and Stimulates Its Transcriptional Activity.
C. Wasylyk, S. E. Schlumberger, P. Criqui-Filipe, and B. Wasylyk (2002)
Mol. Cell. Biol. 22, 2687-2702
   Abstract »    Full Text »    PDF »
Mapping the Unique Activation Function 3 in the Progesterone B-receptor Upstream Segment. TWO LXXLL MOTIFS AND A TRYPTOPHAN RESIDUE ARE REQUIRED FOR ACTIVITY.
L. Tung, T. Shen, M. G. Abel, R. L. Powell, G. S. Takimoto, C. A. Sartorius, and K. B. Horwitz (2001)
J. Biol. Chem. 276, 39843-39851
   Abstract »    Full Text »    PDF »
Pot1, the Putative Telomere End-Binding Protein in Fission Yeast and Humans.
P. Baumann and T. R. Cech (2001)
Science 292, 1171-1175
   Abstract »    Full Text »
beta -Cell Differentiation Factor Nkx6.1 Contains Distinct DNA Binding Interference and Transcriptional Repression Domains.
R. G. Mirmira, H. Watada, and M. S. German (2000)
J. Biol. Chem. 275, 14743-14751
   Abstract »    Full Text »    PDF »
The N-terminal Region of the Human Progesterone A-receptor. STRUCTURAL ANALYSIS AND THE INFLUENCE OF THE DNA BINDING DOMAIN.
D. L. Bain, M. A. Franden, J. L. McManaman, G. S. Takimoto, and K. B. Horwitz (2000)
J. Biol. Chem. 275, 7313-7320
   Abstract »    Full Text »    PDF »
Phosphorylation represses Ets-1 DNA binding by reinforcing autoinhibition.
D. O. Cowley and B. J. Graves (2000)
Genes & Dev. 14, 366-376
   Abstract »    Full Text »
Auto-Inhibition of Ets-1 Is Counteracted by DNA Binding Cooperativity with Core-Binding Factor alpha 2.
T. L. Goetz, T.-L. Gu, N. A. Speck, and B. J. Graves (2000)
Mol. Cell. Biol. 20, 81-90
   Abstract »    Full Text »
Auto-Inhibition and Partner Proteins, Core-Binding Factor beta (CBFbeta ) and Ets-1, Modulate DNA Binding by CBFalpha 2 (AML1).
T.-L. Gu, T. L. Goetz, B. J. Graves, and N. A. Speck (2000)
Mol. Cell. Biol. 20, 91-103
   Abstract »    Full Text »
Characterization of ESE-2, a Novel ESE-1-related Ets Transcription Factor That Is Restricted to Glandular Epithelium and Differentiated Keratinocytes.
P. Oettgen, K. Kas, A. Dube, X. Gu, F. Grall, U. Thamrongsak, Y. Akbarali, E. Finger, J. Boltax, G. Endress, et al. (1999)
J. Biol. Chem. 274, 29439-29452
   Abstract »    Full Text »    PDF »
Regulation of Cell Cycle Transcription Factor Swi4 through Auto-Inhibition of DNA Binding.
K. Baetz and B. Andrews (1999)
Mol. Cell. Biol. 19, 6729-6741
   Abstract »    Full Text »    PDF »
The Net Repressor Is Regulated by Nuclear Export in Response to Anisomycin, UV, and Heat Shock.
C. Ducret, S.-M. Maira, A. Dierich, and B. Wasylyk (1999)
Mol. Cell. Biol. 19, 7076-7087
   Abstract »    Full Text »    PDF »
Inhibition of Ets-1 DNA Binding and Ternary Complex Formation between Ets-1, NF-kappa B, and DNA by a Designed DNA-binding Ligand.
L. A. Dickinson, J. W. Trauger, E. E. Baird, P. B. Dervan, B. J. Graves, and J. M. Gottesfeld (1999)
J. Biol. Chem. 274, 12765-12773
   Abstract »    Full Text »    PDF »
Regulation of DNA Binding Activity and Nuclear Transport of B-Myb in Xenopus Oocytes.
G. Humbert-Lan and T. Pieler (1999)
J. Biol. Chem. 274, 10293-10300
   Abstract »    Full Text »    PDF »
Functional Domains of c-myc Promoter Binding Protein 1 Involved in Transcriptional Repression and Cell Growth Regulation.
A. K. Ghosh, R. Steele, and R. B. Ray (1999)
Mol. Cell. Biol. 19, 2880-2886
   Abstract »    Full Text »    PDF »
Transcriptional Activation by ETS and Leucine Zipper-Containing Basic Helix-Loop-Helix Proteins.
G. Tian, B. Erman, H. Ishii, S. S. Gangopadhyay, and R. Sen (1999)
Mol. Cell. Biol. 19, 2946-2957
   Abstract »    Full Text »    PDF »
The Highly Conserved beta -Hairpin of the Paired DNA-Binding Domain Is Required for Assembly of Pax-Ets Ternary Complexes.
W. Wheat, D. Fitzsimmons, H. Lennox, S. R. Krautkramer, L. N. Gentile, L. P. McIntosh, and J. Hagman (1999)
Mol. Cell. Biol. 19, 2231-2241
   Abstract »    Full Text »    PDF »
Characterization of the Human Endothelial Nitric-oxide Synthase Promoter.
F. Karantzoulis-Fegaras, H. Antoniou, S.-L. M. Lai, G. Kulkarni, C. D'Abreo, G. K. T. Wong, T. L. Miller, Y. Chan, J. Atkins, Y. Wang, et al. (1999)
J. Biol. Chem. 274, 3076-3093
   Abstract »    Full Text »    PDF »
The Kidney-expressed Winged Helix Transcription Factor FREAC-4 Is Regulated by Ets-1. A POSSIBLE ROLE IN KIDNEY DEVELOPMENT.
A. Cederberg, M. Hulander, P. Carlsson, and S. Enerback (1999)
J. Biol. Chem. 274, 165-169
   Abstract »    Full Text »    PDF »
Inhibition of RNA polymerase II transcription in human cells by synthetic DNA-binding ligands.
L. A. Dickinson, R. J. Gulizia, J. W. Trauger, E. E. Baird, D. E. Mosier, J. M. Gottesfeld, and P. B. Dervan (1998)
PNAS 95, 12890-12895
   Abstract »    Full Text »    PDF »
Differential Importin-alpha Recognition and Nuclear Transport by Nuclear Localization Signals within the High-Mobility-Group DNA Binding Domains of Lymphoid Enhancer Factor 1 and T-Cell Factor 1.
M. G. Prieve, K. L. Guttridge, J. Munguia, and M. L. Waterman (1998)
Mol. Cell. Biol. 18, 4819-4832
   Abstract »    Full Text »
Synergistic activation of transcription by nuclear factor Y and sterol regulatory element binding protein.
S. M. Jackson, J. Ericsson, R. Mantovani, and P. A. Edwards (1998)
J. Lipid Res. 39, 767-776
   Abstract »    Full Text »
Identification of Redox-sensitive Cysteines in GA-binding Protein-alpha That Regulate DNA Binding and Heterodimerization.
Y. Chinenov, T. Schmidt, X.-Y. Yang, and M. E. Martin (1998)
J. Biol. Chem. 273, 6203-6209
   Abstract »    Full Text »    PDF »
ETS-Mediated Cooperation between Basic Helix-Loop-Helix Motifs of the Immunoglobulin µ Heavy-Chain Gene Enhancer.
W. Dang, X.-h. Sun, and R. Sen (1998)
Mol. Cell. Biol. 18, 1477-1488
   Abstract »    Full Text »
The Structure of GABPalpha /beta : An ETS Domain- Ankyrin Repeat Heterodimer Bound to DNA.
A. H. Batchelor, D. E. Piper, F. C. de la Brousse, S. L. McKnight, and C. Wolberger (1998)
Science 279, 1037-1041
   Abstract »    Full Text »
Two Roles for the DNA Recognition Site of the Klebsiella aerogenes Nitrogen Assimilation Control Protein.
P. J. Pomposiello, B. K. Janes, and R. A. Bender (1998)
J. Bacteriol. 180, 578-585
   Abstract »    Full Text »
Autoinhibition as a Transcriptional Regulatory Mechanism.
B.J. GRAVES, D.O. COWLEY, T.L. GOETZ, J.M. PETERSEN, M.D. JONSEN, and M.E. GILLESPIE (1998)
Cold Spring Harb Symp Quant Biol 63, 621-630
   Abstract »    PDF »
The Ets Transcription Factors Interact with Each Other and with the c-Fos/c-Jun Complex via Distinct Protein Domains in a DNA-dependent and -independent Manner.
J. P. Basuyaux, E. Ferreira, D. Stehelin, and G. Buttice (1997)
J. Biol. Chem. 272, 26188-26195
   Abstract »    Full Text »    PDF »
Conformational Changes and Stabilization Induced by Ligand Binding in the DNA-binding Domain of the E2 Protein from Human Papillomavirus.
L. M. T. R. Lima and G. de Prat-Gay (1997)
J. Biol. Chem. 272, 19295-19303
   Abstract »    Full Text »    PDF »
Yeast hormone response element assays detect and characterize GRIP1 coactivator-dependent activation of transcription by thyroid and retinoid nuclear receptors.
P. G. Walfish, T. Yoganathan, Y.-F. Yang, H. Hong, T. R. Butt, and M. R. Stallcup (1997)
PNAS 94, 3697-3702
   Abstract »    Full Text »    PDF »
Interaction of Human T-cell Lymphotropic Virus Type I Tax, Ets1, and Sp1 in Transactivation of the PTHrP P2 Promoter.
J. Dittmer, C. A. Pise-Masison, K. E. Clemens, K.-S. Choi, and J. N. Brady (1997)
J. Biol. Chem. 272, 4953-4958
   Abstract »    Full Text »    PDF »
Sp3 Is a Bifunctional Transcription Regulator with Modular Independent Activation and Repression Domains.
B. Majello, P. De Luca, and L. Lania (1997)
J. Biol. Chem. 272, 4021-4026
   Abstract »    Full Text »    PDF »
New Insights on DNA Recognition by ets Proteins from the Crystal Structure of the PU.1 ETS Domain-DNA Complex.
F. Pio, R. Kodandapani, C.-Z. Ni, W. Shepard, M. Klemsz, S. R. McKercher, R. A. Maki, and K. R. Ely (1996)
J. Biol. Chem. 271, 23329-23337
   Abstract »    Full Text »    PDF »
Pip, a lymphoid-restricted IRF, contains a regulatory domain that is important for autoinhibition and ternary complex formation with the Ets factor PU.1..
A L Brass, E Kehrli, C F Eisenbeis, U Storb, and H Singh (1996)
Genes & Dev. 10, 2335-2347
   Abstract »    PDF »
A Novel Family of Developmentally Regulated Mammalian Transcription Factors Containing the TEA/ATTS DNA Binding Domain.
P. Jacquemin, J.-J. Hwang, J. A. Martial, P. Dolle, and I. Davidson (1996)
J. Biol. Chem. 271, 21775-21785
   Abstract »    Full Text »    PDF »
Pax-5 (BSAP) recruits Ets proto-oncogene family proteins to form functional ternary complexes on a B-cell-specific promoter..
D Fitzsimmons, W Hodsdon, W Wheat, S M Maira, B Wasylyk, and J Hagman (1996)
Genes & Dev. 10, 2198-2211
   Abstract »    PDF »
The product of the mouse nude locus, Whn, regulates the balance between epithelial cell growth and differentiation..
J L Brissette, J Li, J Kamimura, D Lee, and G P Dotto (1996)
Genes & Dev. 10, 2212-2221
   Abstract »    PDF »
The EVES motif mediates both intermolecular and intramolecular regulation of c-Myb..
A B Dash, F C Orrico, and S A Ness (1996)
Genes & Dev. 10, 1858-1869
   Abstract »    PDF »
p53: puzzle and paradigm..
L J Ko and C Prives (1996)
Genes & Dev. 10, 1054-1072
   PDF »
Transcription revisited: a commentary on the 1995 Cold Spring Harbor Laboratory meeting, "Mechanisms of Eukaryotic Transcription"..
S L McKnight (1996)
Genes & Dev. 10, 367-381
   PDF »
MRG1 Expression in Fibroblasts Is Regulated by Sp1/Sp3 and an Ets Transcription Factor.
B. Han, N. Liu, X. Yang, H. B. Sun, and Y.-C. Yang (2001)
J. Biol. Chem. 276, 7937-7942
   Abstract »    Full Text »    PDF »
PU.1-mediated Transcription Is Enhanced by HMG-I(Y)-dependent Structural Mechanisms.
R. T. Lewis, A. Andreucci, and B. S. Nikolajczyk (2001)
J. Biol. Chem. 276, 9550-9557
   Abstract »    Full Text »    PDF »
DNA Binding by the ETS-domain Transcription Factor PEA3 Is Regulated by Intramolecular and Intermolecular Protein{middle dot}Protein Interactions.
A. Greenall, N. Willingham, E. Cheung, D. S. Boam, and A. D. Sharrocks (2001)
J. Biol. Chem. 276, 16207-16215
   Abstract »    Full Text »    PDF »
Physical Interaction and Functional Synergy between Glucocorticoid Receptor and Ets2 Proteins for Transcription Activation of the Rat Cytochrome P-450c27 Promoter.
J. Mullick, H. K. Anandatheerthavarada, G. Amuthan, S. V. Bhagwat, G. Biswas, V. Camasamudram, N. K. Bhat, S. E. P. Reddy, V. Rao, and N. G. Avadhani (2001)
J. Biol. Chem. 276, 18007-18017
   Abstract »    Full Text »    PDF »
ERM Transactivation Is Up-regulated by the Repression of DNA Binding after the PKA Phosphorylation of a Consensus Site at the Edge of the ETS Domain.
J.-L. Baert, C. Beaudoin, L. Coutte, and Y. de Launoit (2002)
J. Biol. Chem. 277, 1002-1012
   Abstract »    Full Text »    PDF »
Inhibitory Module of Ets-1 Allosterically Regulates DNA Binding through a Dipole-facilitated Phosphate Contact.
H. Wang, L. P. McIntosh, and B. J. Graves (2002)
J. Biol. Chem. 277, 2225-2233
   Abstract »    Full Text »    PDF »



To Advertise     Find Products


Science. ISSN 0036-8075 (print), 1095-9203 (online)