title: BAP1 regulates cell cycle progression through E2F1 target genes and mediates transcriptional silencing via H2A monoubiquitination in uveal melanoma cells.
abstract: Uveal melanoma (UM) is the most common form of primary intraocular malignancy in adult and has the tendency to metastasize. BAP1 mutations are frequently found in UM and are associated with a poor prognosis. The role of BAP1 in cell cycle regulation is currently a research highlight, but its underlying mechanism is not well understood. Here, we report that BAP1 knockdown can lead to G1 arrest and is accompanied by a decrease in the expression of S phase genes in OCM1 cells. Furthermore, in chromatin immunoprecipitation experiments, BAP1 could bind to E2F1 responsive promoters and the localization of BAP1 to E2F1-responsive promoters is host cell factor-1 dependent. Moreover, BAP1 knockdown leads to increased H2AK119ub1 levels on E2F responsive promoters. Together, these results provide new insight into the mechanisms of BAP1 in cell cycle regulation.
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Pan
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
authors.forename: Renbing
authors.initials: R
authors.lastname: Jia
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
authors.forename: Leilei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
authors.forename: Shiqiong
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
authors.forename: He
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China. Electronic address: geshengfang@sjtu.edu.cn.
authors.forename: Shengfang
authors.initials: S
authors.lastname: Ge
authors.affiliation: Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. Electronic address: xux2@mskcc.org.
authors.forename: Xiaoliang Leon
authors.initials: XL
authors.lastname: Xu
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China. Electronic address: fanxq@sh163.net.
authors.forename: Xianqun
authors.initials: X
authors.lastname: Fan
mesh_terms: D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D047369:Chromatin Immunoprecipitation; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism*; D014604:Uveal Neoplasms / Q000235:genetics / Q000378:metabolism*; D000098943:Uveal Melanoma
chemical_list: C400134:BAP1 protein, human; D050687:E2F1 Transcription Factor; D025521:Tumor Suppressor Proteins; D043222:Ubiquitin Thiolesterase
keywords: BAP1; Cell cycle; E2F1; H2AK119ub1; Uveal melanoma