GSE112979
Genome-wide occupancy of the CEH-60 and UNC-62 Transcription Factors in Caenorhabditis elegans
Animals integrate metabolic, developmental, and environmental information before committing key resources to reproduction.  In C. elegans, adult animals reallocate key fat stores from intestinal cells to the germline via lipoproteins to promote reproduction.  I identified the evolutionarily conserved homeodomain transcription factor CEH-60/PBX as a potent regulator of lipid homeostasis, longevity, and stress response pathways.  To gain a comprehensive view of CEH-60 transcriptional activity, I profiled the transcriptomes of ceh-60 mutants by mRNA-Seq and identified genome-wide CEH-60 binding sites by ChIP-Seq.  These approaches revealed that several homeostatic pathways are directly controlled by the CEH-60 transcription factor.  CEH-60 functions cooperatively with UNC-62/MEIS in the intestine to directly activate lipoprotein genes while simultaneously repressing genes involved in stress responses, including the innate immune and oxidative stress responses.  Thus in wild-type animals, CEH-60 serves as a molecular switch that promotes reproduction (i.e., lipoproteins) while repressing stress response and longevity pathways. This study identifies a new key regulator of fat metabolism, longevity, and stress response pathways during normal C. elegans development. Overall design: The genome-wide binding sites for CEH-60 and UNC-62 (isoform 7a) were identified by high-throughput sequencing.