title: A new kinetochore component CENP-W interacts with the polycomb-group protein EZH2 to promote gene silencing.
abstract: 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.
authors.affiliation: Department of Microbiology and Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Wansoo
authors.initials: W
authors.lastname: Koh
authors.affiliation: Department of Microbiology and Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Byoungwoo
authors.initials: B
authors.lastname: Park
authors.affiliation: Department of Microbiology and Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University, Daejeon 305-764, Republic of Korea. Electronic address: leesoojin@cnu.ac.kr.
authors.forename: Soojin
authors.initials: S
authors.lastname: Lee
mesh_terms: D002843:Chromatin / Q000737:chemistry / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D000071221:Enhancer of Zeste Homolog 2 Protein; D020868:Gene Silencing; D017930:Genes, Reporter; D057809:HEK293 Cells; D006367:HeLa Cells; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018386:Kinetochores / Q000737:chemistry / Q000378:metabolism*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D009363:Neoplasm Proteins; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D055550:Protein Stability; D015398:Signal Transduction; D014157:Transcription Factors; D014162:Transfection
chemical_list: C534000:CENPW protein, human; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D009363:Neoplasm Proteins; C430461:SUZ12 protein, human; D014157:Transcription Factors; D008156:Luciferases; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; D008239:Lysine
keywords: CENP-W; EZH2; Gene silencing; Kinetochore; Oncogene; PRC2