The role of Polycomb-group genes (Pc-G) in maintaining the repressed state of Hox genes is evolutionarily conserved from Drosophila to mammals at both structural and functional level. Pc-G proteins form at least two biochemically separable complexes, Esc-E(Z) and Pc-Ph, which appear to have distinct functions in the repression mediated by Pc-G. The Esc-E(Z) complex consists of Extra sex combs(Esc) and Enhancer of zeste [E(Z)]. The Pc-Ph complex consists the products of Pc, Posterior sex combs(Psc), polyhomeotic(ph), and Sex combs on midleg(Scm). In C. elegans only the homologs of E(Z) and Esc have been identified, and are encoded by
mes-2 and
mes-6, respectively.However, instead in regulating Hox gene expression, the function of
mes-2 and
mes-6 is mainly limited to germline development and silencing of tandem transgenic arrays. Homologs of other Pc-G proteins have not been identified in C. elegansgenome. How the repressed state of Hox gene is maintained in C. elegans is unknown. We have isolated one mutation,
sop-2(
bx91), which causes ectopic expression of all four Hox cluster genes,
lin-39,
ceh-13,
mab-5 and
egl-5, resulting in massive homeotic transformations. For example, the development of a pair of seam cells, V1 to V6, is affected in
sop-2(
bx91)mutants. During normal development, V1 to V4 produce alae, whereas V5 and V6 generate 6 pairs of male sensory organs in the tail, called rays. V5 generates ray 1. V6 gives rise to rays 2 to 6. In
sop-2 males, rays as well as little fan-like cuticular structures, derived from anterior seam cells V1-V4, are formed in anterior body region, and V5 generates one or more ectopic rays. The anterior descendants of V6 often adopt the fate of posterior descendants of V6 in
sop-2mutants, resulting in duplication of rays. Generation of ectopic rays from V1-V5 and duplication of V6-rays are dependent on
mab-5and egl-5 activity.
sop-2 also regulates the expression of
lin-39 in specifying serotonergic neurons in the male ventral cord. Like Pc-Gmutants,
sop-2(
bx91)also causes other defects that may not be due to the ectopic expression of Hox genes. For example,
bx91causes larval lethality at 25 degree, Muv, and partial hermaphrodite to male sex transformation. We found that
sop-2encodes a novel protein with no clear motifs. However, the C-terminal of SOP-2 has a weak similarity to a SPM domain, which is also present in and required for the function of Pc-G proteins Ph and Scm. A highly conserved Proline in this domain has been mutated to Serine in
bx91, suggesting that this domain is important for
sop-2 function. Like the expression of Pc-G genes in other systems,
sop-2 is widely expressed and its product forms speckled domains in the rim of the nucleus. All these studies suggest that a highly divergent Polycomb like complex may be existed in C. elegans to fulfill the Pc-Ph function. We are currently performing yeast two-hybrid to identify the SOP-2 interacting proteins.