The TRA-1 transcription factor binds TRA-2 to regulate sexual fates in Caenorhabditis elegans.
The tra-1 and tra-2 sex-determining genes promote female fates in Caenorhabditis elegans. Classical genetic studies placed tra-1 as the terminal regulator of the pathway with tra-2 acting upstream as a regulator of regulators of tra-1. Here we report the surprising result that the TRA-1 transcription factor binds the intracellular domain of the TRA-2 membrane protein. This binding is dependent on the MX regulatory domain, a region of the TRA-2 intracellular domain shown previously to be critical for the onset of hermaphrodite spermatogenesis. The functional importance of the TRA-1-TRA-2 physical interaction is supported by genetic interactions between tra-1(0) and tra-2(mx) mutations: a reduction of tra-1 gene dose from two copies to one copy enhances the tra-2(mx) feminization phenotype, but has no apparent somatic effect. In Caenorhabditis briggsae, we also find an MX-dependent interaction between Cb-TRA-1 and Cb-TRA-2, but intriguingly, no cross-species interactions are seen. The conservation of the TRA-1- TRA-2 interaction underscores its importance in sex determination.
Wang
S
S
Department of Biochemistry, University of Wisconsin-Madison and Howard Hughes Medical Institute, 53706-1544, USA.
Kimble
J
J
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins; D017124:Conserved Sequence; D017931:DNA Primers; D004268:DNA-Binding Proteins; D012734:Disorders of Sex Development; D005260:Female; D005854:Germ Cells; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011994:Recombinant Proteins; D016415:Sequence Alignment; D012733:Sex Differentiation / Q000502:physiology*; D013045:Species Specificity; D013091:Spermatogenesis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
D029742:Caenorhabditis elegans Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D015801:Helminth Proteins; D008565:Membrane Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; C121025:tra-1 protein, C elegans; C076107:tra-2 protein, C elegans