Hox genes specify cell fates in successive antero-posterior body domains in vertebrates, insects and nematodes (1,2). Polycomb and trithorax group genes are responsible for the initiation and maintenance of Hox gene expression. Nematode homologues of these genes have been discovered and their function is being studied in several labs. We are interested in the function of a domain which is shared between trithorax and polycomb members: the SET domain. This domain which is shared between antagonistic proteins is very conserved and may play an important role in the assembly of either transcriptional activating or repressing protein complexes during development (3). In C. elegans , the 130 amino acid SET motif is present in the polycomb group of proteins (4) including MES-2, a protein similar to E(z) (5). It is also present in SET-1 (T26A5.7), which is predicted to be a 288 residue protein. We have examined the expression pattern of
set-1 in worms carrying a GFP reporter transgene. Early in development,
set-1 is expressed in the majority of cells, its expression being more and more restricted as development progress. The
set-1 gene has been shown to be expressed in seam cells and in vulval cells as well as in the male tail. This expression pattern of
set-1 is reminiscent of the expression pattern of the ensemble of Hox genes (6). The change in the pattern with the GFP-fusion construct is consistent with the variation of transcript levels during development. RNA inactivation has revealed a marked Vab phenotype. The weakest reproducible phenotype observed is a progressive paralysis with adult onset. To study further the role of
set-1 in Hox gene expression, we are injecting
set-1 dsRNA in Hox-LacZ transgenic worms (the kind gifts of C. Kenyon). Also, we are currently screening a bank of UV-TMP mutant worms, using the Barstead protocol, in the hope of obtaining a strain in which
set-1 is knocked out. 1/ Kenyon C. (1994). Cell 78, 175-180 2/ Emmons S. W. (1996). Nature 382, 301-302 3/ Laible et al. (1997). EMBO J. 16, 3219-3232 4/ Korf I., Fan Y.A., Strome S. (1998) Development 125, 2469-2478 5/ Holdeman R., Nehrt S., Strome S. (1998) Development 125, 2457-2467 6/ Wang et al., (1993). Cell 74, 29-42