The nuclear hormone receptor SEX-1 is an X-chromosome signal that determines nematode sex

Nature. 1998 Nov 12;396(6707):168-73. doi: 10.1038/24164.


Organisms in many phyla determine sexual fate by distinguishing one X chromosome from two. Here we use the model organism Caenorhabditis elegans to dissect such an X-chromosome-counting mechanism in molecular detail. In this nematode, several genes on the X chromosome called X signal elements communicate X-chromosome dose by controlling the activity of the sex-determination gene xol-1. xol-1 specifies male (XO) fate when active and hermaphrodite (XX) fate when inactive. The only X signal element described so far represses xol-1 post-transcriptionally, but xol-1 is repressed in XX animals by transcriptional and post-transcriptional mechanisms. Here we identify a nuclear-hormone-receptor homologue, SEX-1, that regulates the transcription of xol-1. We show that sex-1 is vital to X-chromosome counting: changing sex-1 gene dose in XX or XO embryos causes sexual transformation and death from inadequate dosage compensation (the hermaphrodite-specific process that equalizes X-gene expression between the sexes). The SEX-1 protein acts directly on xol-1, associating with its promoter in vivo and repressing xol-1 transcription in XX embryos. Thus, xol-1 is the direct molecular target of the primary sex-determination signal, and the dose of a nuclear hormone receptor helps to communicate X-chromosome number to determine nematode sex.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans Proteins*
  • Chromosome Mapping
  • Disorders of Sex Development / genetics
  • Dosage Compensation, Genetic
  • Female
  • Gene Expression Regulation, Developmental
  • Genes, Helminth
  • Helminth Proteins / genetics*
  • Helminth Proteins / physiology*
  • Male
  • Molecular Sequence Data
  • Mutation
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / physiology
  • Repressor Proteins / genetics
  • Repressor Proteins / physiology*
  • Sex Determination Processes*
  • Signal Transduction
  • X Chromosome*


  • Caenorhabditis elegans Proteins
  • Helminth Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Repressor Proteins
  • sex-1 protein, C elegans
  • XOL-1 protein, C elegans

Associated data

  • GENBANK/AF049869