Temporal regulation of foregut development by HTZ-1/H2A.Z and PHA-4/FoxA

PLoS Genet. 2006 Sep 29;2(9):e161. doi: 10.1371/journal.pgen.0020161. Epub 2006 Aug 11.

Abstract

The histone variant H2A.Z is evolutionarily conserved and plays an essential role in mice, Drosophila, and Tetrahymena. The essential function of H2A.Z is unknown, with some studies suggesting a role in transcriptional repression and others in activation. Here we show that Caenorhabditis elegans HTZ-1/H2A.Z and the remodeling complex MYS-1/ESA1-SSL-1/SWR1 synergize with the FoxA transcription factor PHA-4 to coordinate temporal gene expression during foregut development. We observe dramatic genetic interactions between pha-4 and htz-1, mys-1, and ssl-1. A survey of transcription factors reveals that this interaction is specific, and thus pha-4 is acutely sensitive to reductions in these three proteins. Using a nuclear spot assay to visualize HTZ-1 in living embryos as organogenesis proceeds, we show that HTZ-1 is recruited to foregut promoters at the time of transcriptional onset, and this recruitment requires PHA-4. Loss of htz-1 by RNAi is lethal and leads to delayed expression of a subset of foregut genes. Thus, the effects of PHA-4 on temporal regulation can be explained in part by recruitment of HTZ-1 to target promoters. We suggest PHA-4 and HTZ-1 coordinate temporal gene expression by modulating the chromatin environment.

Publication types

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

MeSH terms

  • Adenosine Triphosphatases / physiology
  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / embryology*
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / metabolism
  • Caenorhabditis elegans Proteins / physiology*
  • DNA-Binding Proteins / metabolism
  • Digestive System / embryology*
  • Digestive System / metabolism
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental
  • Histone Acetyltransferases / physiology
  • Histones / metabolism
  • Histones / physiology*
  • Models, Biological
  • Molecular Sequence Data
  • Pharynx / embryology
  • Pharynx / metabolism
  • Promoter Regions, Genetic
  • Saccharomyces cerevisiae Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / physiology*
  • Sequence Homology, Amino Acid
  • Trans-Activators / metabolism
  • Trans-Activators / physiology*

Substances

  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • Histones
  • Htz1 protein, S cerevisiae
  • Pha-4 protein, C elegans
  • Saccharomyces cerevisiae Proteins
  • Trans-Activators
  • Histone Acetyltransferases
  • MYS-1 protein, C elegans
  • Adenosine Triphosphatases
  • SSL-1 protein, C elegans