Comparative sequence analysis between C. elegans and C. briggsae has proved to be an immensely useful tool in genome annotation. We have used comparative genomics to identify a small (122bp), conserved non-coding element (CNE) in
bro-1 , a homologue of human CBF? which functions with the RUNX gene
rnt-1 (RUNX and CBF? form a well-known transcriptional partnership, regulating cell proliferation and differentiation during the development of several organisms) . Deletion of the CNE from a
bro-1 ::DsRed2 reporter construct significantly changes the expression pattern of the construct, and abolishes its ability to rescue
bro-1 mutants. Furthermore, the
bro-1 CNE can drive GFP expression in the seam cells and rescues the
bro-1 mutant phenotype when used to drive a
bro-1 cDNA::GFP reporter construct. Therefore this CNE is both necessary and sufficient to drive correct
bro-1 expression in seam cells. We have performed a yeast one-hybrid screen using this
bro-1 enhancer element as bait and identified the GATA transcription factor
elt-1 as a putative regulator of
bro-1 , supporting our predictions based on binding site analysis.
elt-1 is known to be required for the correct development and maintenance of the seam (Smith et al., 2005 J. Cell Sci. 118:5709-19) and
elt-1 RNAi animals show similarities to
bro-1 and
rnt-1 mutants. However, both the details of the pathway in which
elt-1 works and the cellular basis of its role in the seam are unclear. Lineage analysis on
elt-1 RNAi worms has revealed that
elt-1 works in at least two ways and is required for both the identity and proliferative ability of cells in the seam lineage. The similarities between
elt-1 RNAi and
bro-1 phenotypes, and the additional specific phenotypes seen in
elt-1 RNAi animals, coupled with our biochemical analyses, support our view that
elt-1 is a direct upstream regulator of
bro-1 .