Authors: Vandamme, Julien; Lettier, Gaelle; Sidoli, Simone; Di Schiavi, Elia; Norregaard Jensen, Ole; Salcini, Anna Elisabetta
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.
Keywords: Animals; *Caenorhabditis elegans/genetics/growth & development; *Caenorhabditis elegans Proteins/genetics/metabolism; Cell Differentiation; Embryonic Development/*genetics; Epigenesis, Genetic; Fertility/genetics; Gene Expression Regulation, Developmental; Histone Demethylases/genetics/metabolism; *Histones/genetics/metabolism; Jumonji Domain-Containing Histone Demethylases/genetics/metabolism; Methylation; RNA Interference|
Journal: PLoS Genet Volume: 8 Issue: 5 Pages: e1002647 Date: May 10, 2012 PMID: 22570628 |
Vandamme, Julien, Lettier, Gaelle, Sidoli, Simone, Di Schiavi, Elia, Norregaard Jensen, Ole, Salcini, Anna Elisabetta (2012) The C. elegans H3K27 demethylase UTX-1 is essential for normal development, independent of its enzymatic activity. PLoS Genet 8: e1002647.
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