Ets-1 binds cooperatively to the palindromic Ets-binding sites in the p53 promoter.
Due to its autoinhibition for DNA binding, the Ets-1 transcription factor must interact with partners to enhance its affinity for DNA. In a study on the stromelysin-1 promoter, we showed that Ets-1 binds cooperatively to two Ets-binding sites (EBS) organized in palindrome, thereby circumventing the need for a binding partner to counteract autoinhibition. This leads to the formation of an Ets-1-DNA-Ets-1 ternary complex necessary for promoter activation. Here we show that Ets-1 also binds cooperatively to the EBS palindrome of the human p53 promoter, despite the presence of a degenerate EBS to which Ets-1 cannot otherwise bind. Transcriptional transactivation through this palindrome fully correlates to Ets-1 binding. Thus, the cooperative binding model that we initially proposed for the stromelysin-1 promoter may be a general mechanism of Ets-1 binding to palindromic EBS separated by 4bp and a way to counteract binding site degeneracy.
Baillat
David
D
CNRS Unité Mixte de Recherche 8161, Institut de Biologie de Lille, Institut Pasteur de Lille, Universités de Lille 1 and Lille 2, IFR 142, B.P. 447, 1 rue du Pr. Calmette, 59021 Lille Cedex, France.
Laitem
Clélia
C
Leprivier
Gabriel
G
Margerin
Charline
C
Aumercier
Marc
M
D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D011401:Promoter Regions, Genetic; D050784:Proto-Oncogene Protein c-ets-1 / Q000378:metabolism*; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
C494041:ETS1 protein, human; D050784:Proto-Oncogene Protein c-ets-1; D016159:Tumor Suppressor Protein p53