A circulatory transcriptional regulation among daf-9, daf-12, and daf-16 mediates larval development upon cholesterol starvation in Caenorhabditis elegans.
C. elegans shows dauer-like larvae formation upon cholesterol starvation (CS), but the genetic epistasis among abnormal dauer formation (daf) genes during the process remains unclear. To clarify the genetic interactions among daf-9, daf-12, and daf-16 in this process, mRNA levels of these genes upon CS were measured. CS increased the mRNA levels of daf-9, daf-12, and daf-16. CS also induced DAF-16 nuclear localization, which was positively and negatively regulated by DAF-12 and DAF-9 activities, respectively. Activated DAF-16, a FOXO transcription factor, enhanced daf-12 but suppressed daf-9 expression, whereas DAF-9 inhibited daf-12 expression. Concomitantly, CS-induced larval arrest was regulated positively by DAF-12 and DAF-16, but negatively by DAF-9. The larval arrest in daf-9 mutant was suppressed by daf-12 RNAi, placing DAF-12 downstream of DAF-9. These results altogether suggest that circulatory mutual regulation among daf-9, daf-12, and daf-16 at the expression level mediates cholesterol signal to control larval development upon CS.
Jeong
Myung-Hwan
MH
Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul, South Korea.
Kawasaki
Ichiro
I
Shim
Yhong-Hee
YH
D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D002784:Cholesterol / Q000172:deficiency / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism*; D051858:Forkhead Transcription Factors; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics; D007814:Larva / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D009154:Mutation; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics
D029742:Caenorhabditis elegans Proteins; C410905:DAF-12 protein, C elegans; D051858:Forkhead Transcription Factors; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol; C486228:DAF-9 protein, C elegans