Polycomb recessive complex 2 (PRC2) plays a central roles in chromatin compaction and remodeling. EZH2, the catalytic subunit of PRC2, is frequently overexpressed in many human tumors. Together with another essential core component, SUZ12, EZH2 trimethylates histone H3 on lysine 27 (H3K27me3). CENP-W was originally identified as a putative oncogene overexpressed in various human tumors, and later characterized as an essential factor for the formation of functional kinetochore during mitosis. In this study, we found that CENP-W associates with EZH2 to subsequently enhance the protein stability of EZH2. Chromatin immunoprecipitation revealed that ectopically expressed CENP-W bound the promoter of EZH2 target genes to enhance EZH2-mediated transcriptional repression, possibly by facilitating the recruitment of EZH2 to its target genes. Collectively, this study suggests CENP-W is a novel kinetochore component that may be involved in the EZH2-mediated silencing machinery. (C) 2015 Elsevier Inc. All rights reserved.