This study used 34 human prostate biopsies and chromatin immunoprecipitation (ChIP) assays to investigate the interactions between H3K27me3 and gene promoter in prostate cancer. ChIP coupled with promoter microarrays enabled us to determine the entire spectrum of in vivo DNA binding sites of the H3K27me3 repressive mark. Identifying region-specific H3K27me3 patterns also helps address additional questions, such as how these observations may resolve or at least suggest causal relationships between histone methylation and prostate cancer progression.