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Nucleic Acids Research, 2000, Vol. 28, No. 18 3433-3441
© 2000 Oxford University Press

Modeling of DNA local parameters predicts encrypted architectural motifs in Xenopus laevis ribosomal gene promoter

Magali Roux-Rouquie and Monique Marilley1,*

GENATLAS - Service de Génétique Médicale, Hôpital Necker-Tour La voisier, 149 rue de Sèvres, 75015 Paris, France and 1Laboratoire de Régulation Génique et Fonctionnelle and Microscopie Champ Proche - UPRES 2059, Faculté de Médecine, 27 boulevard Jean Moulin, Université de la Méditerranée, 13385 Marseille cedex 5, France

We have modeled local DNA sequence parameters to search for DNA architectural motifs involved in transcription regulation and promotion within the Xenopus laevis ribosomal gene promoter and the intergenic spacer (IGS) sequences. The IGS was found to be shaped into distinct topological domains. First, intrinsic bends split the IGS into domains of common but different helical features. Local parameters at inter-domain junctions exhibit a high variability with respect to intrinsic curvature, bendability and thermal stability. Secondly, the repeated sequence blocks of the IGS exhibit right-handed supercoiled structures which could be related to their enhancer properties. Thirdly, the gene promoter presents both inherent curvature and minor groove narrowing which may be viewed as motifs of a structural code for protein recognition and binding. Such pre-existing deformations could simply be remodeled during the binding of the transcription complex. Alternatively, these deformations could pre-shape the promoter in such a way that further remodeling is facilitated. Mutations shown to abolish promoter curvature as well as intrinsic minor groove narrowing, in a variant which maintained full transcriptional activity, bring circumstantial evidence for structurally-preorganized motifs in relation to transcription regulation and promotion. Using well documented X.laevis rDNA regulatory sequences we showed that computer modeling may be of invaluable assistance in assessing encrypted architectural motifs. The evidence of these DNA topological motifs with respect to the concept of structural code is discussed.

* To whom correspondence should be addressed. Tel: +33 4 91 79 48 60; Fax: +33 4 91 79 48 60; Email: monique.marilley@medecine.univ-mrs.fr


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