RRC ID 4203
著者 Peden E, Kimberly E, Gengyo-Ando K, Mitani S, Xue D.
タイトル Control of sex-specific apoptosis in C. elegans by the BarH homeodomain protein CEH-30 and the transcriptional repressor UNC-37/Groucho.
ジャーナル Genes Dev
Abstract 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.
巻・号 21(23)
ページ 3195-207
公開日 2007-12-1
DOI 10.1101/gad.1607807
PII 21/23/3195
PMID 18056429
PMC PMC2081983
MeSH Amino Acid Sequence Animals Animals, Genetically Modified Apoptosis / genetics Apoptosis / physiology* Base Sequence Caenorhabditis elegans / cytology* Caenorhabditis elegans / embryology Caenorhabditis elegans / genetics Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / physiology* Caspases / genetics Caspases / physiology DNA, Helminth / genetics DNA-Binding Proteins / genetics DNA-Binding Proteins / physiology Female Gene Expression Regulation, Developmental Genes, Helminth Homeodomain Proteins / genetics Homeodomain Proteins / physiology* Male Models, Biological Mutation POU Domain Factors / genetics POU Domain Factors / physiology Repressor Proteins / genetics Repressor Proteins / physiology Sequence Homology, Amino Acid Sequence Homology, Nucleic Acid Sex Characteristics Transcription Factors / genetics Transcription Factors / physiology* X Chromosome / genetics
IF 9.527
引用数 46
WOS 分野 GENETICS & HEREDITY DEVELOPMENTAL BIOLOGY CELL BIOLOGY
リソース情報
線虫 tm272 tm2157