The bromodomain protein LEX-1 acts with TAM-1 to modulate gene expression in C. elegans

Mol Genet Genomics. 2007 Nov;278(5):507-18. doi: 10.1007/s00438-007-0265-6. Epub 2007 Jul 6.

Abstract

In many organisms, repetitive DNA serves as a trigger for gene silencing. However, some gene expression is observed from repetitive genomic regions such as heterochromatin, suggesting mechanisms exist to modulate the silencing effects. From a genetic screen in C. elegans, we have identified mutations in two genes important for expression of repetitive sequences: lex-1 and tam-1. Here we show that lex-1 encodes a protein containing an ATPase domain and a bromodomain. LEX-1 is similar to the yeast Yta7 protein, which maintains boundaries between silenced and active chromatin. tam-1 has previously been shown to encode a RING finger/B-box protein that modulates gene expression from repetitive DNA. We find that lex-1, like tam-1, acts as a class B synthetic multivulva (synMuv) gene. However, since lex-1 and tam-1 mutants have normal P granule localization, it suggests they act through a mechanism distinct from other class B synMuvs. We observe intragenic (interallelic) complementation with lex-1 and a genetic interaction between lex-1 and tam-1, data consistent with the idea that the gene products function in the same biological process, perhaps as part of a protein complex. We propose that LEX-1 and TAM-1 function together to influence chromatin structure and to promote expression from repetitive sequences.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenosine Triphosphatases / physiology*
  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / physiology*
  • Cell Cycle Proteins
  • Cloning, Molecular
  • DNA / metabolism
  • Gene Expression Regulation*
  • Gene Expression Regulation, Developmental*
  • Gene Silencing
  • Heterozygote
  • Models, Biological
  • Molecular Sequence Data
  • Mutation
  • Nuclear Proteins / physiology*
  • Phenotype
  • Recombination, Genetic
  • Sequence Homology, Amino Acid

Substances

  • Caenorhabditis elegans Proteins
  • Cell Cycle Proteins
  • Nuclear Proteins
  • TAM-1 protein, C elegans
  • DNA
  • Adenosine Triphosphatases
  • Lex-1 protein, C elegans