The Mi-2 nucleosome-remodeling protein LET-418 is targeted via LIN-1/ETS to the promoter of lin-39/Hox during vulval development in C. elegans

Dev Biol. 2007 Jun 15;306(2):469-79. doi: 10.1016/j.ydbio.2007.03.026. Epub 2007 Mar 24.

Abstract

The fate of the vulval cells in Caenorhabditis elegans is specified, at least in part, through a highly conserved RTK/Ras mediated signaling cascade that negatively regulates the activity of the ETS-like transcription factor LIN-1. The Hox gene lin-39 functions downstream of both, the LIN-3/RTK/Ras pathway and LIN-1 and plays a pivotal role in controlling vulva cell competence and induction. Here we show that LET-418, a C. elegans ortholog of the human NuRD component Mi-2, negatively modulates the activity of lin-39. LET-418 interacts in vivo with specific regions in the promoter of lin-39 and this interaction depends on LIN-1. Our data provide evidence for a model in which LIN-1 recruits LET-418/Mi-2 as co-repressor to the promoter of lin-39, thereby restricting its activity to the basal levels required in the vulva precursor cells (VPCs) for normal vulval development. Thus, our data suggest that the interaction between LIN-1 and LET-418/Mi-2 may link RTK/Ras signaling with chromatin remodeling and gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / chemistry
  • Caenorhabditis elegans Proteins / metabolism
  • Caenorhabditis elegans Proteins / physiology*
  • Chromatin / metabolism
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / physiology*
  • Female
  • Gene Expression Regulation, Developmental*
  • Homeodomain Proteins / physiology*
  • Models, Genetic
  • Mutation
  • Nucleosomes / metabolism*
  • Phenotype
  • Promoter Regions, Genetic*
  • RNA Interference
  • Transcription Factors / metabolism*
  • Vulva / embryology*

Substances

  • Caenorhabditis elegans Proteins
  • Chromatin
  • DNA-Binding Proteins
  • Homeodomain Proteins
  • LET-418 protein, C elegans
  • Lin-1 protein, C elegans
  • Nucleosomes
  • Transcription Factors
  • lin-39 protein, C elegans