A ONECUT homeodomain protein communicates X chromosome dose to specify Caenorhabditis elegans sexual fate by repressing a sex switch gene

Genetics. 2007 Nov;177(3):1621-37. doi: 10.1534/genetics.106.061812. Epub 2007 Aug 24.

Abstract

Sex is determined in Caenorhabditis elegans through a dose-dependent signal that communicates the number of X chromosomes relative to the ploidy, the number of sets of autosomes. The sex switch gene xol-1 is the direct molecular target of this X:A signal and integrates both X and autosomal components to determine sexual fate. X chromosome number is relayed by X signal elements (XSEs) that act cumulatively to repress xol-1 in XX animals, thereby inducing hermaphrodite fate. Ploidy is relayed by autosomal signal elements (ASEs), which counteract the single dose of XSEs in XO animals to activate xol-1 and induce the male fate. Our goal was to identify and characterize new XSEs and further analyze known XSEs to understand the principles by which a small difference in the concentration of an intracellular signal is amplified to induce dramatically different developmental fates. We identified a new XSE, the ONECUT homeodomain protein CEH-39, and showed that it acts as a dose-dependent repressor of xol-1 transcript levels. Unexpectedly, most other XSEs also repress xol-1 predominantly, but not exclusively, at the transcript level. The twofold difference in X dose between XO and XX animals is translated into the male vs. hermaphrodite fate by the synergistic action of multiple, independent XSEs that render xol-1 active or inactive, primarily through transcriptional regulation.

Publication types

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

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Chromosome Mapping
  • DNA Primers / genetics
  • DNA, Helminth / genetics
  • Dosage Compensation, Genetic
  • Female
  • Gene Dosage
  • Genes, Helminth
  • Male
  • Models, Biological
  • Onecut Transcription Factors / genetics
  • Onecut Transcription Factors / metabolism*
  • RNA Interference
  • Sex Determination Processes*
  • Sex Differentiation / genetics
  • Signal Transduction
  • X Chromosome / genetics*

Substances

  • Caenorhabditis elegans Proteins
  • DNA Primers
  • DNA, Helminth
  • Onecut Transcription Factors
  • XOL-1 protein, C elegans