Genome-wide analysis of androgen receptor (AR) SUMOylation effects on gene expression (HEK293).

ABSTRACT: Androgen receptor (AR) plays an important regulatory role during prostate cancer development. ARM-bM-^@M-^Ys transcriptional activity is regulated by androgenic ligands, but also by post-translational modifications. To study the role of the AR SUMOylation in genuine chromatin environment, we compared androgen-regulated gene expression and AR chromatin occupancy in PC-3 prostate cancer and HEK293 cell lines stably expressing wild-type (wt) or SUMOylation site-mutated AR (AR-K386R,K520R). Our genome-wide gene expression analyses reveal that the SUMOylation modulates the AR function in a target gene and pathway selective manner. The transcripts that are differentially regulated by androgen and SUMOylation are linked to cellular movement, cell death, cellular proliferation, cellular development and cell cycle. In line with these data, SUMOylation mutant AR cells proliferate faster and are more sensitive to apoptosis. Moreover, ChIP-seq analyses show that the SUMOylation modulates the chromatin occupancy of AR on many loci in a fashion that parallels with their differential androgen-regulated expression. De novo motif analyses show that other transcription factor-binding motifs are differentially enriched at the wtAR- and the AR-K386R,K520R-preferred genomic binding positions. Taken together, our data indicate that SUMOylation does not simply repress the AR activity, but it regulates ARM-bM-^@M-^Ys interaction with the chromatin and the receptorM-bM-^@M-^Ys target gene selection. Isogenic HEK293 cells stably expressing wild-type AR (wtAR) or SUMOylation-defective AR (AR-K2R) were treated 24 h with 10 nM R1881 or vehicle (EtOH). All conditions were performed in triplicate. The effect on gene expression was assessed by microarray.

ORGANISM(S): Homo sapiens

SUBMITTER: PM-CM-$ivi Sutinen 

PROVIDER: E-GEOD-54137 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress