Control of sex-specific apoptosis in C. elegans by the BarH homeodomain protein CEH-30 and the transcriptional repressor UNC-37/Groucho.
Apoptosis is essential for proper development and tissue homeostasis in metazoans. It plays a critical role in generating sexual dimorphism by eliminating structures that are not needed in a specific sex. The molecular mechanisms that regulate sexually dimorphic apoptosis are poorly understood. Here we report the identification of the ceh-30 gene as a key regulator of sex-specific apoptosis in Caenorhabditis elegans. Loss-of-function mutations in ceh-30 cause the ectopic death of male-specific CEM neurons. ceh-30 encodes a BarH homeodomain protein that acts downstream from the terminal sex determination gene tra-1, but upstream of, or in parallel to, the cell-death-initiating gene egl-1 to protect CEM neurons from undergoing apoptosis in males. The second intron of the ceh-30 gene contains two adjacent cis-elements that are binding sites for TRA-1A and a POU-type homeodomain protein UNC-86 and acts as a sensor to regulate proper specification of the CEM cell fate. Surprisingly, the N terminus of CEH-30 but not its homeodomain is critical for CEH-30's cell death inhibitory activity in CEMs and contains a conserved eh1/FIL domain that is important for the recruitment of the general transcriptional repressor UNC-37/Groucho. Our study suggests that ceh-30 defines a critical checkpoint that integrates the sex determination signal TRA-1 and the cell fate determination and survival signal UNC-86 to control the sex-specific activation of the cell death program in CEMs through the general transcription repressor UNC-37.
Department of Molecular, Cellular and Developmental Biology University of Colorado, Boulder, Colorado 80309, USA.
Erin
E
Peden
Elizabeth
E
Kimberly
Keiko
K
Gengyo-Ando
Shohei
S
Mitani
Ding
D
Xue
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000196:embryology / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D020169:Caspases / Q000235:genetics / Q000502:physiology; D018509:DNA, Helminth / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D008297:Male; D008954:Models, Biological; D009154:Mutation; D050809:POU Domain Factors / Q000235:genetics / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D012727:Sex Characteristics; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014960:X Chromosome / Q000235:genetics
D029742:Caenorhabditis elegans Proteins; D018509:DNA, Helminth; D004268:DNA-Binding Proteins; C112486:EGL-1 protein, C elegans; D018398:Homeodomain Proteins; D050809:POU Domain Factors; D012097:Repressor Proteins; D014157:Transcription Factors; C121025:tra-1 protein, C elegans; C106184:unc-37 protein, C elegans; C081539:unc-86 protein, C elegans; D020169:Caspases; C089223:ced-3 protein, C elegans