Nf-y. C. Elegans As A Pcg Genes Regulate Hox Gene Egl-5 Expression

NF-Y is an evolutionarily conserved heterotrimeric transcription factor,which is present in all eukaryotes.The physiological function of NF-Y in developing animals,however,has yet to be determined due to lack of an animal model with abrogation of endogenousNF-Y.In this study we demonstrated that mutations in Cenf-ya1,Cenf-yb,and Cenf-yc,encoding the C.elegans homologs of NF-Y,cause ectopic expression of Hox gene eg1-5(ortholog of Drosophila Abdominal-B).In addition,mutations in Cenf-ya1 cause defects in the generation of several male specific structures,which may due to the deregulation of a set of genes required for their pattern formation.Our results not only indicated that NF-Y functions both as transcriptional activator and repressor but also unraveled the physiological function of NF-Y in pattern formation.The differential gene expression pattern in distinct cells is established by the orchestrated action of many transcriptional factors,which interact with cis-acting DNA sequence elements.Uncovering the transcriptional network mediated by each transcription factor is crucial for revealing the mechanisms underlying the complex pattern formation during animal development.NF-Y,one of the most abundant transcription factors in eukaryotes, specifically recognizes the CCAAT boxes located in gene promoters.NF-Y is evolutionarily conserved from yeast to human and has distinct functions in different organisms.The yeast HAP2/3/5 NF-Y complex activates cytochromes and other mitochondria genes involved in respiratory pathway,whose gene promoters contain the CCAAT boxes.In mammalian cells,NF-Y is a ubiquitous and constitutive factor,regulating numerous genes involved in various biological processes.Consistently,the CCAAT box has been shown to be one of the most widespread DNA elements in the promoters of mammalian genes.One analysis indicates that it is present in 64%of the promoter regions in 1031 human genes with preferentially located -105 to -70 with respect to the transcriptional start site.NF-Y may activate gene expression through its role in facilitating the binding of TFIID to the core promoters.However,the physiological function of NF-Y in multicellular organisms remains to be determined due to lack of an animal model with abrogation of endogenous NF-Y.Hox genes,encoding conserved homeodomain-containing transcription factors,control the positional identities of cells along the anterior-posterior axis.Inappropriate expression of Hox genes leads to homeotic transformations, in which body structures are lost or duplicated.Thus,identification of factors required for the establishment of the spatially restricted expression domains of Hox genes is critical for understanding the means by which the cellular positional identities are specified during animal development.In this study we demonstrated that the expression of C.elegans Hox gene eg1-5is globally repressed by the NF-Y complex.NF-Y also plays an important role in the generation of several male specific structures through regulating a set of genes required for their pattern formation.Our studies unraveled the physiological function of NF-Y in developing animals and also provided insight in the evolution of the function of NF-Y in eukaryotes.