Title

Transcriptional regulation of the eff-1 gene

Date of Completion

January 2005

Keywords

Biology, Molecular|Biology, Genetics

Degree

Ph.D.

Abstract

In C. elegans, cell fusion requires the activity of the eff-1 gene (e&barbelow;pithelial f&barbelow;usion f&barbelow;ailure). Nematodes that are mutant for this gene fail to fuse their hypodermal, vulval, and pharyngeal cells during development. Ectopic expression of eff-1 is lethal to embryos and larvae, suggesting that precise temporal regulation of eff-1 expression in these specific cell types is important for normal development. Part of this regulation occurs at the transcriptional level. Therefore, studying the transcriptional regulation of eff-1 presents one avenue for understanding the biological phenomenon of cell fusion. ^ Deletion mutational analyses of the eff-1 promoter revealed discrete cis-acting regulatory domains that control tissue-specific activity. In particular, domains that control eff-1 promoter activity in various tissues and organs have been identified for the hypodermis, vulva, and pharynx. Through yeast one-hybrid experiments, potential candidate transcription factors have been identified that may regulate eff-1 transcription in a tissue-specific manner. ^ PHA-4, a transcription factor that directs pharynx morphogenesis may act directly upon eff-1 to drive pharyngeal expression. Interestingly, a stochastic "all-or-none" effect on pharyngeal expression is observed when two putative PHA-4 binding sites in the eff-1 promoter are mutated. The similar expression of Peff-1p::gfp by each binucleate cell in the pharynx of a given animal indicates the existence of a "noise-damping" mechanism that tightly coordinates gene expression levels among these cells of quite distinct lineage. ^