We demonstrated that RORα2 is a direct substrate for SETD7 and that lysine methylation of RORα2 underlies transcriptional activation of RORα2 in the regulation of tumorigenic target genes in PCa cells, including CTNND1. In the event of methylation, both methylation and subsequent binding to coactivator complex are required steps for the coordinated regulation of this process. This evidence concerns the gene CTNND1 and posterior cortical atrophy.