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Direct cooperation between androgen receptor and E2F1 reveals a common regulation mechanism for androgen-responsive genes in prostate cells

D. M. Altintas1, M. S. Shukla2, D. Goutte-Gattat3, D. Angelov2, J. P. Rouault1, S. Dimitrov3 and J. Samarut1,4,a

1Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Claude Bernard Lyon 1, CNRS, INRA, École Normale Supérieure de Lyon, F-69346 Lyon cedex 7, France

2Laboratoire de Biologie Moléculaire de la Cellule, Université de Lyon, CNRS, École Normale Supérieure de Lyon, F-69346 Lyon, France

3Université Joseph Fourier – Grenoble 1, INSERM Institut Albert Bonniot U823, 38042 Grenoble cedex 9, France

4Hospices Civils de Lyon, 69229 Lyon, France

aCorresponding author:

This article was published in Molecular Endocrinology.

Mol. Endocrinol., 26(9):1531–1541. [abstract]


We have studied the regulation of ATAD2 gene expression by androgens in prostate cells. ATAD2 is a coactivator of the androgen receptor (AR) and the MYC protein. We showed that ATAD2 expression is directly regulated by AR via an AR binding sequence (ARBS) located in the distal enhancer of its regulator region. The gene is also regulated by the E2F1 transcription factor. Using knockdown and chromatin immunoprecipitation technique approaches, we could demonstrate that AR and E2F1 functionally collaborate and physically interact between each other. From the analysis of chromatin conformation, we conclude that this cooperation results from a chromatin looping over the ATAD2 promoter region between the ARBS and E2F1 binding site in an androgen-dependant manner. Furthermore, we could show that several genes overexpressed in prostate cancer and potentially involved in several aspects of tumor development have an ARBS and an E2F1 binding site in their regulatory regions and exhibit the same mechanism of regulation by both transcription factors as ATAD2.

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