The RIP140 gene is a transcriptional target of E2F1.
RIP140 is a transcriptional coregulator involved in energy homeostasis and ovulation which is controlled at the transcriptional level by several nuclear receptors. We demonstrate here that RIP140 is a novel target gene of the E2F1 transcription factor. Bioinformatics analysis, gel shift assay, and chromatin immunoprecipitation demonstrate that the RIP140 promoter contains bona fide E2F response elements. In transiently transfected MCF-7 breast cancer cells, the RIP140 promoter is transactivated by overexpression of E2F1/DP1. Interestingly, RIP140 mRNA is finely regulated during cell cycle progression (5-fold increase at the G1/S and G2/M transitions). The positive regulation by E2F1 requires sequences located in the proximal region of the promoter (-73/+167), involves Sp1 transcription factors, and undergoes a negative feedback control by RIP140. Finally, we show that E2F1 participates in the induction of RIP140 expression during adipocyte differentiation. Altogether, this work identifies the RIP140 gene as a new transcriptional target of E2F1 which may explain some of the effect of E2F1 in both cancer and metabolic diseases.
IRCM, Institut de Recherche en Cancérologie de Montpellier, and INSERM, U896, Montpellier, France.
Aurélie
A
Docquier
Patrick
P
Augereau
Marion
M
Lapierre
Pierre-Olivier
PO
Harmand
Eric
E
Badia
Jean-Sébastien
JS
Annicotte
Lluis
L
Fajas
Vincent
V
Cavaillès
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D050687:E2F1 Transcription Factor / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics*; D000078723:Nuclear Receptor Interacting Protein 1; D011401:Promoter Regions, Genetic
D048868:Adaptor Proteins, Signal Transducing; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C000627127:NRIP1 protein, human; D009687:Nuclear Proteins; D000078723:Nuclear Receptor Interacting Protein 1