title: The histone demethylase UTX enables RB-dependent cell fate control.
abstract: Trimethylation of histone H3 on Lys 27 (H3K27me3) is key for cell fate regulation. The H3K27me3 demethylase UTX functions in development and tumor suppression with undefined mechanisms. Here, genome-wide chromatin occupancy analysis of UTX and associated histone modifications reveals distinct classes of UTX target genes, including genes encoding Retinoblastoma (RB)-binding proteins. UTX removes H3K27me3 and maintains expression of several RB-binding proteins, enabling cell cycle arrest. Genetic interactions in mammalian cells and Caenorhabditis elegans show that UTX regulates cell fates via RB-dependent pathways. Thus, UTX defines an evolutionarily conserved mechanism to enable coordinate transcription of a RB network in cell fate control.
authors.affiliation: Howard Hughes Medical Institute and Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Jordon K
authors.initials: JK
authors.lastname: Wang
authors.forename: Miao-Chih
authors.initials: MC
authors.lastname: Tsai
authors.forename: Gino
authors.initials: G
authors.lastname: Poulin
authors.forename: Adam S
authors.initials: AS
authors.lastname: Adler
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Chen
authors.forename: Helen
authors.initials: H
authors.lastname: Liu
authors.forename: Yang
authors.initials: Y
authors.lastname: Shi
authors.forename: Howard Y
authors.initials: HY
authors.lastname: Chang
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism; D005786:Gene Expression Regulation; D016678:Genome / Q000235:genetics; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D009369:Neoplasms / Q000378:metabolism; D056286:Retinoblastoma Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002843:Chromatin; D056286:Retinoblastoma Binding Proteins; D056484:Jumonji Domain-Containing Histone Demethylases; C523761:Kdm6b protein, mouse