title: Ets-1 p51 and p42 isoforms differentially modulate Stromelysin-1 promoter according to induced DNA bend orientation.
abstract: The Stromelysin-1 gene promoter contains a palindrome of two Ets-binding sites (EBS) that bind the p51 and p42 isoforms of the human Ets-1-transcription factor. A previous study established that full gene transactivation is associated with a ternary complex consisting of two p51 bound to the two EBS on the promoter. p42, only able to bind one of the two EBS, induces only very weak activity. Here, we investigate the mechanism by which the Stromelysin-1 promoter discriminates between p51 and p42. The differential stoichiometry of the two Ets-1 isoforms arises from the Stromelysin-1 EBS palindrome. The ternary complex requires the presence of two inhibitory domains flanking the DNA-binding domain and the ability to form an intramolecular autoinhibition module. Most importantly, the p51-ternary and the p42-binary complexes induce DNA curvatures with opposite orientations. These results establish that differential DNA bending, via p51 and p42 differential binding, is correlated with the Stromelysin-1 promoter activation process.
authors.affiliation: CNRS UMR 8161, Institut de Biologie de Lille, Université de Lille 1 and Lille 2, IFR 142, BP 447, 59021 Lille Cedex, France.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Leprivier
authors.forename: David
authors.initials: D
authors.lastname: Baillat
authors.forename: Agnès
authors.initials: A
authors.lastname: Begue
authors.forename: Brigitte
authors.initials: B
authors.lastname: Hartmann
authors.forename: Marc
authors.initials: M
authors.lastname: Aumercier
mesh_terms: D001665:Binding Sites; D004247:DNA / Q000737:chemistry*; D006801:Humans; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D050784:Proto-Oncogene Protein c-ets-1 / Q000737:chemistry / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D020033:Protein Isoforms; D050784:Proto-Oncogene Protein c-ets-1; D004247:DNA; D019278:Matrix Metalloproteinase 3