title: The C. elegans H3K27 demethylase UTX-1 is essential for normal development, independent of its enzymatic activity.
abstract: Epigenetic modifications influence gene expression and provide a unique mechanism for fine-tuning cellular differentiation and development in multicellular organisms. Here we report on the biological functions of UTX-1, the Caenorhabditis elegans homologue of mammalian UTX, a histone demethylase specific for H3K27me2/3. We demonstrate that utx-1 is an essential gene that is required for correct embryonic and postembryonic development. Consistent with its homology to UTX, UTX-1 regulates global levels of H3K27me2/3 in C. elegans. Surprisingly, we found that the catalytic activity is not required for the developmental function of this protein. Biochemical analysis identified UTX-1 as a component of a complex that includes SET-16(MLL), and genetic analysis indicates that the defects associated with loss of UTX-1 are likely mediated by compromised SET-16/UTX-1 complex activity. Taken together, these results demonstrate that UTX-1 is required for many aspects of nematode development; but, unexpectedly, this function is independent of its enzymatic activity.
authors.affiliation: Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
authors.forename: Julien
authors.initials: J
authors.lastname: Vandamme
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Lettier
authors.forename: Simone
authors.initials: S
authors.lastname: Sidoli
authors.forename: Elia
authors.initials: E
authors.lastname: Di Schiavi
authors.forename: Ole
authors.initials: O
authors.lastname: Nørregaard Jensen
authors.forename: Anna Elisabetta
authors.initials: AE
authors.lastname: Salcini
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D047108:Embryonic Development / Q000235:genetics*; D044127:Epigenesis, Genetic; D005298:Fertility / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D056466:Histone Demethylases / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics / Q000378:metabolism; D008745:Methylation; D034622:RNA Interference
chemical_list: D029742:Caenorhabditis elegans Proteins; D006657:Histones; D056466:Histone Demethylases; D056484:Jumonji Domain-Containing Histone Demethylases; C575118:UTX-1 protein, C elegans