The C. elegans H3K27 demethylase UTX-1 is essential for normal development, independent of its enzymatic activity

PLoS Genet. 2012;8(5):e1002647. doi: 10.1371/journal.pgen.1002647. Epub 2012 May 3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans Proteins* / genetics
  • Caenorhabditis elegans Proteins* / metabolism
  • Caenorhabditis elegans* / genetics
  • Caenorhabditis elegans* / growth & development
  • Cell Differentiation
  • Embryonic Development / genetics*
  • Epigenesis, Genetic
  • Fertility / genetics
  • Gene Expression Regulation, Developmental
  • Histone Demethylases / genetics
  • Histone Demethylases / metabolism
  • Histones* / genetics
  • Histones* / metabolism
  • Jumonji Domain-Containing Histone Demethylases / genetics
  • Jumonji Domain-Containing Histone Demethylases / metabolism
  • Methylation
  • RNA Interference

Substances

  • Caenorhabditis elegans Proteins
  • Histones
  • Histone Demethylases
  • Jumonji Domain-Containing Histone Demethylases
  • UTX-1 protein, C elegans