Abstract
We have examined the ability of the full-length estrogen receptor (ER) and the purified estrogen receptor DNA binding domain to bend DNA on binding to estrogen response element (ERE). Purified ER DNA binding domain (DBD) expressed in E. coli, crude human ER expressed in MCF-7 cells, and partially purified human ER expressed in yeast, bound specifically to a series of circularly permuted ERE-containing DNA fragments. Binding of ER to a single ERE induced a reproducible DNA bend of 56°. This was 1.65 fold greater than the 34° bending angle induced by binding of the ER DNA binding domain. The DNA bending angle induced was the same whether the salt-extracted receptor was unoccupied, occupied by 17β-estradiol, or occupied by trans-hydroxytamoxifen. To determine if proteins associated with ER in MCF-7 cells affect the degree of bending, we examined the ability of partially purified human ER, expressed in yeast, to bend DNA. The degree of bending induced by the partially purified yeast ER, and by the crude MCF-7 cell ER, was the same. When two EREs were present in the DNA fragment, 1.2 and 1.55 fold increases in DNA bending were observed for the full-length ER, and for the ER DNA binding domain, respectively. Our demonstration that binding of human estrogen receptor to the ERE induces DNA bending suggests a role for DNA bending in ER-induced transcription activation.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Beato, M (1989): Gene regulation by steroid hormones. Cell 56: 335–344.
Beebe JS, Darling DS and Chin WW (1991): 3,5,3′-Triiodothyronine receptor auxiliary protein (TRAP) enhances receptor binding by interactions within the thyroid hormone response element. Mol Endocrinol 5: 85–93.
Bracco L, Kotlarz D, Kolb A, Diekmann S and Buc H (1989): Synthetic curved DNA sequences can act as transcriptional activators in Escherichia coli. EMBO J 8: 4289–4296.
Brown M and Sharp PA (1990): Human estrogen receptor forms multiple protein DNA complexes. J Biol Chem 265: 11238–11243.
Chang T-C, Nardulli AM, Lew D and Shapiro DJ (1992): The role of estrogen response elements in expression of the Xenopus laevis vitellogenin B1 gene. Mol Endocrinol 6: 346–354.
Chang T-C and DJ Shapiro (1990): An Nf1-related vitellogenin activator element mediates transcription from the estrogen regulated Xenopus laevis vitellogenin promoter. J Biol Chem 265: 8176–8182.
Crothers MR and Crothers DM (1988): DNA sequence determinants of CAP-induced bending and protein binding affinity. Nature 333:824–831.
Crothers DM, Crothers MR and Shrader TS (1991): DNA bending in protein-DNA complexes. Methods Enzymol 208: 118–146.
Curtis SW and Korach KS (1990): Uterine estrogen receptor interaction with estrogen-responsive DNA sequences in vitro: effects of ligand binding on receptor-DNA complexes. Mol Endocrinol 4: 276–286.
Debs RJ, Freedman LP, Edmunds S, Gaensler KL, Dzgnes N and Yamamoto KR (1990): Regulation of gene expression in vivo by liposome-mediated delivery of a purified transcription factor. J Biol Chem 265: 10189–10192.
Dieckman S (1992): Analyzing DNA curvature in Polyacrylamide gels. Methods Enzymol 212: 30–46.
Elliston JF, Falwell SE, Klein-Hitpass L, Tsai SY, Tsai M-J, Parker MG and O’Malley BW (1990): Mechanism of estrogen receptor-dependent transcription in cell-free system. Mol Cell Biol 12: 6607–6612.
Evans RM (1988): The steroid and thyroid hormone receptor superfamily. Science 240: 889–895.
Falwell SE, Lees JA, White R and Parker MG (1990): Characterization and colocalization of steroid binding and dimerization activities in the mouse estrogen receptor. Cell 60: 953–962.
Freedman LP, Yoshinaga SK, Vanderbilt JN and Yamamoto KR (1989): In vitro transcription enhancement by purified derivatives of the glucocorticoid receptor. Science 245: 298–301.
Giese K, Cox J and Grosschedl R (1992): The HMG domain of lymphoid enhancer factor 1 bends DNA and facilitates assembly of functional nucleoprotein structures. Cell 69: 185–195.
Goodman S, Young C-C, Nash H, Savai A and Jernigan R (1990): Bending of DNA by IHF Protein. In Structure and Methods, Volume 2, DNA Protein Complexes and Proteins, RH Sarma and MH Sarma, eds (New York: Adenine Press), pp. 51–62.
Green S, Walter P, Kumar V, Krust A, Bornert J-M, Argos P and P Chambon (1986): Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A. Nature 320: 134–139.
Greene GL, Gilna P, Waterfield M, Baker A, Hort Y and Shine J (1986): Sequence and expression of human estrogen receptor complementary DNA. Science 231: 1150–1154.
Guiochon-Mantel A, Loosfelt H, Ragot T, Bailly A, Atger M, Misrahi M, Perricaudet M and Milgrom E (1988): Receptors bound to antiprogestin form abortive complexes with hormone responsive elements. Nature 336: 695–698.
Hager GL and Archer TK (1991): The interaction of steroid receptors with chromatin, p. 217–234. In: MG Parker (ed), Nuclear hormone receptors: molecular mechanism, cellular functions and clinical abnormalities. Academic Press, San Diego, CA.
Hard T, Kellenbach E, Boelens R, Maler BA, Dahlman K, Freedman LP, Carlstedt-Duke J, Yamamoto KR, Gustafsson J-A and Kaptein R (1990): Solution structure of the glucocorticoid receptor DNA-binding domain. Science 249: 157–160.
Kerppola TK and Curran T (1991): Fos-jun heterodimers and jun homodimers bend DNA in opposite orientations: implications for transcription factor cooperativity. Cell 66: 317–326.
Kim J, Zwieb C, Wu C and Adhya S (1989): Bending of DNA by gene-regulatory proteins: construction and use of a DNA bending vector. Gene 85: 15–23.
Klein-Hitpass L, Tsai SY, Weigel NL, Allan GF, Riley D, Rodriguez R, Schrader WT, Tsai M-J and O’Malley BW (1990): The progesterone receptor stimulates cell-free transcription by enhancing the formation of a stable preinitiation complex. Cell 60: 247–257.
Kumar V, Green S, Stack G, Berry M, Jin J-R and Chambon P (1987): Functional domains of the human estrogen receptor. Cell 51: 941–951.
Kumar V and Chambon P (1988): The estrogen receptor binds tightly to its responsive element as a ligand-induced homodimer. Cell 55: 145–156.
Landy A (1989): Dynamic, structural and regulatory aspects of site-specific recombination. Annu Rev Biochem 58: 913–949.
Lees JA, Falwell SE and Parker MG (1989): Identification of two transactivation domains in the mouse estrogen receptor. Nucleic Acids Res 17: 5477–5488.
Leidig F, Shepard AR, Zhang W, Stelter A, Cattini PA, Baxter JD and Eberhardt NL (1992): Thyroid hormone responsiveness in human growth hormone-related genes: possible correlations with receptor-induced DNA conformational changes. J Biol Chem 267: 913–921.
Liu-Johnson H-N, Crothers MR and Crothers DM (1986): The DNA binding domain and bending angle of E. coli CAP protein. Cell 47: 995–1005.
Lue NF, Buchman AR and Kornberg RD (1989): Activation of yeast RNA polymerase II transcription by a thymidine-rich upstream element in vitro. Proc Natl Acad Sci USA 86:486–490.
Luisi BF, Xu WX, Otwinowski Z, Freedman LP, Yamamoto KR and Sigler PB (1991): Crystallographic analysis of the interaction of the glucocorticoid receptor with DNA. Nature 352: 497–505.
Martinez E and Wahli W (1989): Cooperative binding of estrogen receptor to imperfect estrogen-responsive DNA elements correlates with their synergistic hormone-dependent enhancer activity. EMBO J 8: 3781–3791.
Miesfeld R, Godowski PJ, Maler BA and Yamamoto KR (1987): Glucocorticoid receptor mutants that define a small region sufficient for enhancer activation. Science 236: 423–427.
Mukherjee R and Chambon P (1990): A single-stranded DNA-binding protein promotes the binding of the purified oestrogen receptor to its responsive element. Nucl Acids Res 18: 5713–5716.
Murdoch, FE, Meier DA, Furlow JD, Grunwald K and Gorski J (1990): Estrogen receptor binding to a DNA response element in vitro is not dependent on estradiol. Biochem 29: 8377–8385.
Nardulli AM, Lew D, Erijman L and Shapiro DJ (1991): Purified estrogen receptor DNA binding domain expressed in Escherichia coli activates transcription of an estrogen-responsive promoter in cultured cells. J Biol Chem 266: 24070–24076.
Nardulli AM and Shapiro DJ (1992): Binding of the estrogen receptor DNA-binding domain to the estrogen response element induces DNA bending. Mol Cell Biol 12: 2037–2042.
Nardulli AM, Greene GL and Shapiro DJ (1993): Human estrogen receptor bound to an estrogen response element bends DNA. Mol Endocrinol 7: 331–340.
Nash H (1990): Bending and supercoiling of DNA at the attachment site of bacteriophage lambda. Trends Biochem Sci 15: 222–227.
Nelson WG, Pienta KJ, Barrack ER and Coffey DS (1986): The role of the nuclear matrix in the organization and function of DNA. Annu Rev Biophys Chem 15: 457–475.
Pina B, Hach RJG, Arnemann J, Chalepakis G, Slater EP and Beato M (1990): Hormonal induction of transfected genes depends on DNA topology. Mol Cell Biol 10: 625–633.
Pina B, Bruggemeier U and Beato M (1990): Nucleosome positioning modulates accessibility of regulatory proteins to the Mouse Mammary Tumor Virus promoter. Cell 60: 719–731.
Ponglikitmongkol M, White JH and Chambon P (1990): Synergistic activation of transcription by the human estrogen receptor bound to tandem responsive elements. EMBO J 9: 2221–2231.
Rojo F and Salas M (1991): A DNA curvature can substitute phage d29 regulatory protein p4 when acting as a transcriptional repressor. EMBO J 10:3429–3438.
Schreck R, Zorbas H, Winnacker E-L and Baeuerle PA (1980): The NF-KB transcription factor induces DNA bending which is modulated by its 65-kD subunit. Nucl Acids Res 18: 6497–6502.
Schule R, Muller M, Kattschmidt C and Renkawitz R (1988): Many transcription factors interact synergistically with steroid receptors. Science 242: 1418–1420.
Schwabe JWR, Neuhaus D and Rhodes D (1990): Solution structure of the DNA-binding domain of the oestrogen receptor. Nature 348: 458–461.
Seiler-Tuyns A, Walker P, Martinez E, Merillat AM, Givel F and Wahli W (1986): Identification of estrogen-responsive DNA sequences by transient expression experiments in a human breast cancer cell line. Nucl Acids Res 14: 8755–8770.
Shuey DJ and Parker CS (1986): Bending of promoter DNA on binding of heat shock transcription factor. Nature (London) 323: 459–561.
Spelsberg TC, Littlefield BA, Seelke R, Dani GM, Toyoda H, Boyd-Leinen P, Thrall CT and Kon OL (1983): Role of specific chromosomal proteins and DNA sequences in the nuclear binding sites for steroid receptors. Recent Prog Horm Res 39: 463–513.
Strahle U, Schmid W and Schutz G (1988): Synergistic action of the glucocorticoid receptor with transcription factors. EMBO J 7: 3389–3395.
Tasset D, Tora L, Fromental C, Scheer E and Chambon P (1990): Distinct classes of transcriptional activating domains function by different mechanisms. Cell 62: 1177–1187.
Thompson JF and Landy A (1988): Empirical estimation of protein-induced DNA bending angles: applications to G site-specific recombination complexes. Nucl Acids Res 16: 9687–9705.
Tzukerman M, Zhang X-K, Hermann T, Wills KN, Graupner G and Pfahl M (1990): The human estrogen receptor has transcriptional activator and repressor functions in the absence of ligand. New Biol 2: 613–620.
Verrijzer CP, van Oosterhout JAWM, van Weperen WW and van de Vliet PC (1991): POU proteins bend DNA via the POU-specific domain. EMBO J 10: 3007–3014.
Vignais M-L and Sentenac A (1989): Asymmetric DNA bending induced by the yeast multifunctional factor TUF. J Biol Chem 264: 8463–8466.
Walker P, Germond JE, Brown-Luedi M, Givel F and Wahli W (1984): Sequence homologies in the region preceding the transcription initiation site of the liver estrogen-responsive vitellogenin and apo-VLDL II genes. Nucl Acids Res 12: 8611–8625.
Waterman ML, Adler S, Nelson C, Greene GL, Evans RM and Rosenfeld MG (1988): A single domain of the estrogen receptor confers deoxyribonucleic acid binding and transcriptional activation of the rat prolactin gene. Mol Endocrinol 2: 14–21.
Weiler IJ, Lew D and Shapiro DJ (1987): The Xenopus laevis estrogen receptor: sequence homology with human and avian receptors and identification of multiple messenger ribonucleic acids. Mol Endocrinol 10: 355–362.
Wu H-M and Crothers DM (1984): The locus of sequence-directed and protein-induced DNA bending. Nature (London) 308: 509–513.
Yang C-C and Nash HA (1989): The interaction of E coli IHF-protein with its specific binding sites. Cell 57: 869–880.
Yu VC, Delsert C, Andersen B, Holloway JM, Devary OV, Nr AM, Kim SY, Boutin J-M, Glass CK and Rosenfeld MG (1991): RXR: a coregulator that enhances binding of retinoic acid, thyroid hormone, and vitamin D receptors to their cognate response elements. Cell 67: 1251–1266.
Zwieb C, Kim J and Adhya S (1989): DNA bending by negative regulatory proteins: gal and lac repressors. Genes and Develop 3: 606–611.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1994 Birkhäuser Boston
About this chapter
Cite this chapter
Shapiro, D.J., Greene, G.L., Nardulli, A.M. (1994). Estrogen Receptor Induced DNA Bending. In: Moudgil, V.K. (eds) Steroid Hormone Receptors: Basic and Clinical Aspects. Hormones in Health and Disease. Birkhäuser Boston. https://doi.org/10.1007/978-1-4615-9849-7_3
Download citation
DOI: https://doi.org/10.1007/978-1-4615-9849-7_3
Publisher Name: Birkhäuser Boston
Print ISBN: 978-1-4615-9851-0
Online ISBN: 978-1-4615-9849-7
eBook Packages: Springer Book Archive