Organ development is a complex process, and a simple model to study this is the C. elegans pharynx. We have previously identified a core sub-set pharyngeal gland expressed genes under the control of the gland specific bHLH transcription factor, HLH-6.
hlh-6 mutants are feeding defective (as are animals were the gland are ablated) suggesting a role in for the glands in feeding.
hlh-6 is under control of several cis-regulatory elements, including the gland expressed element HRL3 (Hlh-6 Regulatory element 3). In addition to regulating
hlh-6, HRL3 directly regulates several other HLH-6 independent gland expressed genes. Interestingly, while both HLH-6 and HRL3 and most of their targets are expressed in all gland cells, there are several targets whose expression is restricted to specific gland cell sub-types. Here we show that several of these targets undergo negative regulation by unique cis-elements in their promoters to achieve these patterns. Here we will discuss one of these genes, Y8A9A.2
Y8A9A.2 is a Thrombospondin-like protein expressed in the
g1p and
g2 gland sub-types. present in the promoter is a consensus HRL3 site, which when mutated results in a complete loss of expression. Also present is a highly conserved 20 bp region, which is necessary and sufficient to repress expression in the
g1a glands. In this region is a highly conserved NHR (Nuclear Hormone Receptor) binding site, and when mutated results in loss of repression in the
g1a gland cells. We tested several NHR genes expressed in the glands, and found a that when Y8A9A.2 is examined in a
nhr-48(-) mutant the result is a similar loss of repression in the
g1a gland cells, suggesting that NHR-48 may be the trans-factor acting to repress expression of Y8A9A.2 in the
g1a cells.
We know gland fates are specified differently from other pharyngeal cell types due to the combinatorial action of various transcriptional repressor and activators. We don't observe a
g1a to
g1p/g2 sub-type fate transformation in
nhr-48(-), suggesting the differences in gland sub-types are the level of differential expression of some of these functional genes, and the understanding how genes like Y8A9A.2 function will ultimately lead to the understanding of the exact role of these subtypes.