Direct Cooperation Between Androgen Receptor and E2F1 Reveals a Common Regulation Mechanism for Androgen-Responsive Genes in Prostate Cells

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 regulatory 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-dependent 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.

The lncRNA SLNCR1 Mediates Melanoma Invasion through a Conserved SRA1-like Region

“…Of these, we focused on AR for several reasons: (1) AP2, ATF2, E2F-1, and EGR directly or indirectly interact with AR (Altintas et al, 2012; Jorgensen and Nilson, 2001; Verger et al, 2001; Zhang et al, 2010), suggesting that enrichment of these probes is a consequence of protein-protein interactions rather than direct interaction with SLNCR1 . (2) Transcriptional network analysis of melanomas over-expressing or knocking down SLNCR1 reveals significant enrichment of AR - regulated genes (Table S4: SLNCR1 knockdown, p-value = 1.45e-59, z-score = 134.17; Table S5: SLNCR1 over-expression, p-value 5.070E-63, z-score = 160.15; MetaCore™, Thomson Reuters).…”

Proto-oncogene Activity of Melanoma Antigen-A11 (MAGE-A11) Regulates Retinoblastoma-related p107 and E2F1 Proteins

“…A threshold model was proposed where genes that regulate cell proliferation or apoptosis are induced by different levels of E2F that act as positive or negative regulators of cell growth (53). Positive and negative cooperation in gene regulation by AR and E2F1 were reported in prostate cancer cells (95)(96)(97). Relative levels of MAGE-A11 and p107 influence AR and E2F1 transcriptional activation or repression.…”

Biphotonic Ionization of DNA: From Model Studies to Cell

“…This procedure, in combination with immunochemical techniques (laser X‐ChIP‐qPCR), was used to detect the presence of specific proteins on DNA sequences of interest in whole cells. These included RNA pol II and the androgen receptor (AR) , as well as RNA pol V and AGO4 in nuclei isolated from plant cells . The above examples demonstrate the utility of the UV laser cross‐linking for gaining relevant structural and conformational information that cannot be obtained using either the conventional UV irradiation or formaldehyde cross‐linking techniques.…”