Using a custom analysis pipeline, we found that both the Top2a-dependent gene set and a set of autism-associated genes maintained by the Simons Foundation for Autism Research (SFARI genes hereafter) are selectively targeted by polycomb repressive complex 2 (PRC2), a regulatory complex responsible for depositing H3K27 trimethylation (H3K27me3). Here, TOP2A is linked to autism.