We use C. elegans male ray development as a model to study how the transcriptional machinery uses developmental information to regulate the expression of Hox genes. Hox genes
mab-5 and
egl-5 are expressed in and required for seam cell V6 to generate 5 rays. The expression of
mab-5 in V6 is activated by the caudal homolog
pal-1 during embryogenesis. The expression of
egl-5 in the V6 lineage is dependent on
mab-5. In
pal-1(
e2091) mutants, V6 rays are missing due to the lack of expression of
mab-5 in V6. To identify new genes regulating Hox gene expression we performed a screen for suppressors of the V6 ray loss phenotype of
pal-1(
e2091), which has a mutation in a putative V6 enhancer element.
sop-3 is one of several suppressors we identified.
sop-3 activates the expression of
mab-5 in V6 by restoring the activity of
pal-1(
e2091).
sop-3 encodes a novel protein with characteristics of transcriptional repressors, including Ala-rich, Pro-rich, and highly charged domains.
sop-3 interacts with a Wnt pathway to regulate the expression of the Hox genes
mab-5 and
egl-5 in the V6 lineage. Mutation of
sop-3 results in the ectopic expression of
mab-5 and
egl-5 and bypasses the requirement of
mab-5 for the activation of
egl-5 in the V6 lineage. The inappropriate expression of
mab-5 and
egl-5 in
sop-3 mutants requires the activity of
bar-1/b-catenin.
sop-3 interacts genetically with
sop-1,
sur-2 and
unc-37.
sop-1 and
sur-2 encode the human TRAP230 and hSur-2 homologs, respectively, which are components of the transcriptional Mediator complex. The multiprotein Mediator complex is required for relaying signals from transcriptional regulators to RNA Pol II.
unc-37 encodes the homolog of the general corepressor Groucho. A
sop-3 mutation causes a synthetic lethal phenotype with mutations in
sop-1,
sur-2 and the weak allele of
unc-37(
e262).
sop-3 also functions with
sop-1,
sur-2 and
unc-37 to play a positive role in the generation of V6 rays. Our results suggest
sop-3 interacts with components of the transcriptional mediator complex and the C. elegans general corepressor Groucho homolog to regulate gene expression, including Hox genes
mab-5 and
egl-5.