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 |