The nuclear hormone receptor SEX-1 is an X-chromosome signal that determines nematode sex.
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.
Carmi
I
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Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley 94720-3204, USA.
Kopczynski
J B
JB
Meyer
B J
BJ
D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins; D002874:Chromosome Mapping; D012734:Disorders of Sex Development / Q000235:genetics; D004303:Dosage Compensation, Genetic; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth; D015801:Helminth Proteins / Q000235:genetics* / Q000502:physiology*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D019849:Sex Determination Processes; D015398:Signal Transduction; D014960:X Chromosome
D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; C115677:sex-1 protein, C elegans; C091429:XOL-1 protein, C elegans