RT Journal
A1 Hiltunen, Johannes
A1 Helminen, Laura
A1 Aaltonen, Niina
A1 Launonen, Kaisa-Mari
A1 Laakso, Hanna
A1 Malinen, Marjo
A1 Niskanen, Einari A.
A1 Palvimo, Jorma J.
A1 Paakinaho, Ville
T1 Androgen receptor–mediated assisted loading of the glucocorticoid receptor modulates transcriptional responses in prostate cancer cells
JF Genome Research 
JO Genome Research 
YR 2025 
FD August 01 
VO 35 
IS 8 
SP 1717 
OP 1732 
DO 10.1101/gr.280224.124 
UL http://genome.cshlp.org/content/35/8/1717.abstract 
AB Steroid receptors are involved in a wide array of cross talk mechanisms that regulate diverse biological processes, with significant implications in diseases, particularly in cancers. In prostate cancer, indirect cross talk between androgen receptor (AR) and glucocorticoid receptor NR3C1 (also known as GR) is well documented, wherein AR suppression by antiandrogen therapy leads to elevated GR levels, enabling GR to compensate for and replace AR signaling. However, the existence and impact of direct chromatin cross talk between AR and GR in prostate cancer have remained elusive. Here, our genome-wide investigations reveal that AR activation significantly expands GR chromatin binding. Mechanistically, AR induces remodeling of closed chromatin sites, facilitating GR binding to inaccessible sites. Importantly, coactivation of AR and GR results in distinct transcriptional responses at both the cell population and single-cell levels. Pathways affected by these transcriptional changes are generally associated with improved patient survival. Thus, the direct cross talk between AR and GR yields markedly different outcomes from the known role of GR in circumventing AR blockade by antiandrogens.