Document Type

Honors Project

Publication Date

Spring 6-1-2016

Abstract

A degenerative disease-like phenotype, specifically reduction in synaptic protein levels in adult worms, is correlated with loss-of-function of the only RFX transcription factor gene, daf-19, in C. elegans. This gene encodes four known transcription factor isoforms, two of which are correlated with particular functions. The DAF-19C isoform activates genes responsible for cilia development, while DAF-19M is needed for cilia specification in males. A comparison of the transcriptome of daf-19 null and isogenic wild type adult worms suggests both positive and negative regulation of gene expression is correlated with the presence of DAF-19 proteins. We have assessed DAF-19 regulation of gene expression using transcriptional fusion constructs of putative target genes in daf-19 wild type and mutant worms. We have found that at least three genes are repressed by the DAF-19 transcription factor in particular nerve cells. In one case, differential gene expression is seen in sensory neurons while differential expression of two other genes is limited to interneurons. Interestingly, none of these genes have been shown to contain an X-box, the cis-acting sequence used to activate genes involved in cilia formation. These data suggest that DAF-19 has an additional role beyond that of sensory neuron development and specification. Because the daf-19 gene produces at least four related proteins, further experimentation is required to determine which DAF-19 isoform(s) are responsible for repression of gene expression. We are currently using new alleles of daf-19 to determine whether the largest DAF-19 proteins, DAF-19A/B have a role in repressing target gene expression.

Level of Honors

magna cum laude

Department

Biology

Advisor

Elizabeth Ann de Stasio