The TRA-1A sex determination protein of C. elegans regulates sexually dimorphic cell deaths by repressing the egl-1 cell death activator gene.
The hermaphrodite-specific neurons (HSNs) of the nematode Caenorhabditis elegans are generated embryonically in both hermaphrodites and males but undergo programmed cell death in males. The gene egl-1 encodes a BH3-containing cell death activator that is required for programmed cell death in C. elegans. Gain-of-function (gf) mutations in egl-1 cause the inappropriate programmed cell death of the HSNs in hermaphrodites. These mutations lie 5.6 kb downstream of the egl-1 transcription unit and disrupt the binding of the TRA-1A zinc finger protein, the terminal global regulator of somatic sexual fate. This disruption results in the activation of the egl-1 gene in the HSNs not only in males but also in hermaphrodites. Our findings suggest that in hermaphrodites TRA-1A represses egl-1 transcription in the HSNs to prevent these neurons from undergoing programmed cell death.
Conradt
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Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge 02319, USA.
Horvitz
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D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis; D001483:Base Sequence; D001665:Binding Sites; D002107:Caenorhabditis / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins; D018509:DNA, Helminth / Q000737:chemistry / Q000235:genetics; D004268:DNA-Binding Proteins; D012734:Disorders of Sex Development / Q000235:genetics; D005260:Female; D049452:Green Fluorescent Proteins; D015801:Helminth Proteins / Q000235:genetics* / Q000378:metabolism*; D006720:Homozygote; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D009154:Mutation; D009474:Neurons / Q000166:cytology / Q000502:physiology; D009838:Oligodeoxyribonucleotides; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D019849:Sex Determination Processes; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic
D029742:Caenorhabditis elegans Proteins; D018509:DNA, Helminth; D004268:DNA-Binding Proteins; C112486:EGL-1 protein, C elegans; D015801:Helminth Proteins; D008164:Luminescent Proteins; D009838:Oligodeoxyribonucleotides; D012097:Repressor Proteins; D014157:Transcription Factors; C121025:tra-1 protein, C elegans; D049452:Green Fluorescent Proteins