The histone demethylase UTX enables RB-dependent cell fate control.
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.
Wang
Jordon K
JK
Howard Hughes Medical Institute and Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
Tsai
Miao-Chih
MC
Poulin
Gino
G
Adler
Adam S
AS
Chen
Shuzhen
S
Liu
Helen
H
Shi
Yang
Y
Chang
Howard Y
HY
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*
D002843:Chromatin; D056286:Retinoblastoma Binding Proteins; D056484:Jumonji Domain-Containing Histone Demethylases; C523761:Kdm6b protein, mouse