title: The H3K27me3 demethylase UTX in normal development and disease.
abstract: In 2007, the Ubiquitously Transcribed Tetratricopeptide Repeat on chromosome X (UTX) was identified as a histone demethylase that specifically targets di- and tri-methyl groups on lysine 27 of histone H3 (H3K27me2/3). Since then, UTX has been proven essential during normal development, as it is critically required for correct reprogramming, embryonic development and tissue-specific differentiation. UTX is a member of the MLL2 H3K4 methyltransferase complex and its catalytic activity has been linked to regulation of HOX and RB transcriptional networks. In addition, an H3K27me2/3 demethylase independent function for UTX was uncovered in promoting general chromatin remodeling in concert with the BRG1-containing SWI/SNF remodeling complex. Constitutional inactivation of UTX causes a specific hereditary disorder called the Kabuki syndrome, whereas somatic loss of UTX has been reported in a variety of human cancers. Here, we compile the breakthrough discoveries made from the first disclosure of UTX as a histone demethylase till the identification of disease-related UTX mutations and specific UTX inhibitors.
authors.affiliation: Center for Medical Genetics; Ghent University; Ghent, Belgium.
authors.forename: Joni
authors.initials: J
authors.lastname: Van der Meulen
authors.affiliation: Center for Medical Genetics; Ghent University; Ghent, Belgium.
authors.forename: Frank
authors.initials: F
authors.lastname: Speleman
authors.affiliation: Center for Medical Genetics; Ghent University; Ghent, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Van Vlierberghe
mesh_terms: D000015:Abnormalities, Multiple / Q000201:enzymology*; D000818:Animals; D065150:Cellular Reprogramming; D047108:Embryonic Development; D053595:Embryonic Stem Cells / Q000201:enzymology; D005145:Face / Q000002:abnormalities*; D016147:Genes, Tumor Suppressor; D006402:Hematologic Diseases / Q000201:enzymology*; D056466:Histone Demethylases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000201:enzymology*; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015837:Vestibular Diseases / Q000201:enzymology*; D049951:X Chromosome Inactivation
chemical_list: D006657:Histones; D009687:Nuclear Proteins; D056466:Histone Demethylases; C523998:KDM6A protein, human
keywords: H3K27; HOX; Kabuki; MLL2; RB; SWI/SNF; UTX; cancer; embryogenesis; reprogramming