Genome-wide Identification of Binding Sites Defines Distinct Functions for Caenorhabditis Elegans PHA-4/FOXA in Development and Environmental Response

PLoS Genet. 2010 Feb 19;6(2):e1000848. doi: 10.1371/journal.pgen.1000848.

Abstract

Transcription factors are key components of regulatory networks that control development, as well as the response to environmental stimuli. We have established an experimental pipeline in Caenorhabditis elegans that permits global identification of the binding sites for transcription factors using chromatin immunoprecipitation and deep sequencing. We describe and validate this strategy, and apply it to the transcription factor PHA-4, which plays critical roles in organ development and other cellular processes. We identified thousands of binding sites for PHA-4 during formation of the embryonic pharynx, and also found a role for this factor during the starvation response. Many binding sites were found to shift dramatically between embryos and starved larvae, from developmentally regulated genes to genes involved in metabolism. These results indicate distinct roles for this regulator in two different biological processes and demonstrate the versatility of transcription factors in mediating diverse biological roles.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Binding Sites
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / growth & development*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Chromatin Immunoprecipitation
  • Embryo, Nonmammalian / metabolism
  • Environment*
  • Gene Expression Regulation, Developmental
  • Genes, Helminth / genetics
  • Genome, Helminth / genetics*
  • Green Fluorescent Proteins / metabolism
  • Larva / metabolism
  • Protein Binding
  • RNA Polymerase II / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Starvation
  • Survival Analysis
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factors / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • Pha-4 protein, C elegans
  • Recombinant Fusion Proteins
  • Trans-Activators
  • Transcription Factors
  • Green Fluorescent Proteins
  • RNA Polymerase II