The transcriptional activity of the serum response factor (SRF) protein is triggered by its binding to a 10-base-pair DNA consensus sequence designated the CArG box, which is the core sequence of the serum response element (SRE). Sequence-specific recognition of the CArG box by a core domain of 100 amino acid residues of SRF (core-SRF) was asserted to depend almost exclusively on the intrinsic SRE conformation and on the degree of protein-induced SRE bending. Nevertheless, this paradigm was invalidated by a temperature-dependent Raman spectroscopy study of 20-mer oligonucleotides involved in bonding interactions with core-SRF that reproduced both wild type and mutated c-fos SREs. Indeed, the SRE moieties that are complexed with core-SRF exhibit permanent interconversion dynamics between bent and linear conformers. Thus, sequence-specific recognition of the CArG box by core-SRF cannot be explained only in terms of the three-dimensional structure of the SRE. A particular dynamic pairing process discriminates between the wild type and mutated complexes. Specific oscillations of the phosphate charge network of the SRE govern the recognition between both partners rather than an intrinsic set of conformations of the SRE.

ER12 UPMC Université Paris 06 Paris France

Institute of Physics Faculty of Mathematics and Physics Charles University Prague Prague Czech Republic

Laboratoire Jean Perrin UPMC Université Paris 06 CNRS FRE 3231 Paris France

Laboratoire Jean Perrin UPMC Université Paris 06 CNRS FRE 3231 Paris France; ER12 UPMC Université Paris 06 Paris France; Institute of Physics Faculty of Mathematics and Physics Charles University Prague Prague Czech Republic

UR4 UPMC Université Paris 06 Paris France

Zobrazit více v PubMed

Miano JM, Long X, Fujiwara K (2007) Serum response factor: master regulator of the actin cytoskeleton and contractile apparatus. Am. J. Physiol. Cell Physiol. 292: C70–81. PubMed

Treisman R (1987) Identification and purification of a polypeptide that binds to the c-fos serum response element. EMBO J. 6: 2711–2717. PubMed PMC

Chen C-Y, Schwartz R (1997) Competition between negative acting YY1 versus positive acting serum response factor and tinman homologue Nkx-2.5 regulates cardiac alpha-actin promoter activity. Mol. Endocrinol. 11: 812–822. PubMed

Mericskay M, Parlakian A, Porteu A, Dandre F, Bonnet J, et al. (2000) An overlapping CArG/octamer element is required for regulation of desmin gene transcription in arterial smooth muscle cells. Dev. Biol. 226, 192–208. PubMed

Norman C, Runswick M, Pollock R, Treisman R (1988) Isolation and properties of cDNA clones encoding SRF, a transcription factor that binds to the c-fos serum response element. Cell 55: 989–1003. PubMed

Hipskind RA, Rao VN, Mueller CGF, Reddy ESP, Nordheim A (1991) Ets-related protein Elk-1 is homologous to the c-fos regulatory factor p62TCF. Nature 354: 531–534. PubMed

Sharrocks AD, Von Hesler F, Shaw PE (1993) The identification of elements determining the different DNA binding specificities of the MADS box proteins p67SRF and RSRFC4. Nucleic Acids Res. 21: 215–221. PubMed PMC

Schwarz-Sommer Z, Huijser P, Nacken W, Saedler H, Sommer H (1990) Genetic control of flower development by homeotic genes in Antirrhinum majus . Science 250: 931–936. PubMed

Shore P, Sharrocks AD (1995) The MADS-box family of transcription factors. Eur. J. Biochem. 229: 1–13. PubMed

Leung S, Miyamoto NG (1989) Point mutational analysis of the human c-fos serum response factor binding site. Nucleic Acids Res. 17: 1177–1195. PubMed PMC

Mo Y, Ho W, Johnston K, Marmorstein R (2001) Crystal structure of a ternary SAP-1/SRF/c-fos SRE DNA complex. J. Mol. Biol. 314: 495–506. PubMed

Huet A, Parlakian A, Arnaud M-C, Glandières JM, Valat P, et al. (2005) Mechanism of binding of serum response factor to serum response element. FEBS J. 272: 3105–3119. PubMed

Treisman R (1985) Transient accumulation of c-fos RNA following serum stimulation requires a conserved 5' element and c-fos 3' sequences. Cell 42: 889–902. PubMed

Greenberg ME, Siegfried Z, Ziff EB (1987) Mutation of the c-fos gene dyad symmetry element inhibits serum inducibility of transcription in vivo and the nuclear regulatory factor binding in vitro. Mol. Cell. Biol. 7: 1217–1225. PubMed PMC

Štěpánek J, Vincent M, Turpin P-Y, Paulin D, Fermandjian S, et al. (2007) C→G base mutations in the CArG box of c-fos serum response element alter its bending flexibility. Consequences for core-SRF recognition. FEBS J. 274: 2333–2348. PubMed

Gustafson TA, Taylor A, Kedes L (1989) DNA bending is induced by a transcription factor that interacts with the human c-FOS and α-actin promoters. Proc. Nat. Acad. Sci. USA 86: 2162–2166. PubMed PMC

West AG, Shore P, Sharrocks AD (1997) DNA binding by MADS-box transcription factors: a molecular mechanism for differential DNA bending. Mol. Cell. Biol. 17: 2876–2887. PubMed PMC

Pellegrini L, Tan S, Richmond TJ (1995) Structure of serum response factor core bound to DNA. Nature 376: 490–498. PubMed

Štěpánek J, Kopecký V Jr, Mezzetti A, Turpin P- Y, Paulin D, et al. (2010) Structural and dynamic changes of the serum response element and the core domain of serum response factor induced by their association. Biochem. Biophys. Res. Commun. 391: 203–208. 10.1016/j.bbrc.2009.11.032 PubMed DOI

Movileanu L, Benevides JM, Thomas GJ Jr (1999) Temperature dependence of the Raman spectrum of DNA. Part I—Raman signatures of premelting and melting transitions of poly(dA-dT) poly(dA-dT). J. Raman Spectrosc. 30: 637–649. PubMed

Benevides JM, Overman SA, Thomas GJ Jr (2005) Raman, polarized Raman and ultraviolet resonance Raman spectroscopy of nucleic acids and their complexes. J. Raman Spectrosc. 36: 279–299.

Movileanu L, Benevides JM, Thomas GJ Jr (2002) Temperature dependence of the Raman spectrum of DNA. II. Raman signatures of premelting and melting transitions of poly(dA) poly(dT) and comparison with poly(dA-dT) poly(dA-dT). Biopolymers 63: 181–194. PubMed

Deng H, Bloomfield VA, Benevides JM, Thomas GJ Jr (2000) Structural basis of polyamine–DNA recognition: spermidine and spermine interactions with genomic B-DNAs of different GC content probed by Raman spectroscopy. Nucleic Acids Res. 28: 3379–3385. PubMed PMC

Tuma R (2005) Raman spectroscopy of proteins: from peptides to large assemblies. J. Raman Spectrosc. 36: 307–319.

Overman SA, Thomas GJ Jr (1999) Raman markers of nonaromatic side chains in an alpha-helix assembly: Ala, Asp, Glu, Gly, Ile, Leu, Lys, Ser, and Val residues of phage fd subunits. Biochemistry 38: 4018–4027. PubMed

Overman SA, Thomas GJ Jr (1995) Raman spectroscopy of the filamentous virus Ff (fd, fl, M13): structural interpretation for coat protein aromatics. Biochemistry 34: 5440–5451. PubMed

Yu L, Zhu C-X, Tse-Dinh Y-C, Fesik SW (1996) Backbone dynamics of the C-terminal domain of Escherichia coli topoisomerase I in the absence and presence of single-stranded DNA. Biochemistry 35: 9661–9666. PubMed

Shepard W, Soutourina O, Courtois E, England P, Haouz A (2011) Insights into the Rrf2 repressor family—the structure of CymR, the global cysteine regulator of Bacillus subtilis . FEBS J. 278: 2689–2701. 10.1111/j.1742-4658.2011.08195.x PubMed DOI

Nurrish SJ, Treisman R (1995) DNA binding specificity determinants in MADS-box transcription factors. Mol. Cell. Biol. 15: 4076–4085. PubMed PMC

Rohs R, West SM, Sosinsky A, Liu P, Mann RS (2009) The role of DNA shape in protein-DNA recognition. Nature 461: 1248–1253. 10.1038/nature08473 PubMed DOI PMC

Rohs R, Jin X, West SM, Joshi R, Honig B (2010) Origins of specificity in protein–DNA recognition. Annu. Rev. Biochem. 79: 233–269. 10.1146/annurev-biochem-060408-091030 PubMed DOI PMC

Tzeng SR, Kalodimos CG (2012) Protein activity regulation by conformational entropy. Nature 488: 236–240. 10.1038/nature11271 PubMed DOI

Treisman R, Marais R, Wynne J (1992) Spatial flexibility in ternary complexes between SRF and its accessory proteins. EMBO J. 11: 4631–4640. PubMed PMC

Lickwar CR, Mueller F, Hanlon SE, McNally JG, Lieb JD (2012) Genome-wide protein–DNA binding dynamics suggest a molecular clutch for transcription factor function. Nature 484: 251–255. 10.1038/nature10985 PubMed DOI PMC

Polymorphic potential of SRF binding site of c-Fos gene promoter: in vitro study