Worm Breeder's Gazette 11(1): 42
These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.
Mutations in the gene lin-11 cause certain vulval precursor cells ( the 2 cells) to divide symmetrically instead of asymmetrically. Hence, the gene appears to play a role in the ability of one cell to divide asymmetrically to produce daughter cells of two different types. We previously reported the cloning and sequencing of a small region of a putative lin-11 cDNA (WBG 10:3, 33) and the finding that it encodes a homeodomain that is very similar to that of mec-3, a gene involved in the development of the touch neurons (Way and Chalfie, Cell 54, 5, 1988). A 1.7 kb lin-11 cDNA has now been sequenced and the two genes appear to have extensive similarity upstream of the homeodomain. Interestingly, a large percentage of the conserved residues between the two proteins are histidines and cysteines. A comparison of the conserved residues between lin-11 and mec-3 has revealed a repeated motif of the histidine and cysteine residues (see figure). This motif is repeated twice in lin-11 and one and a half times in the published protein sequence of mec-3. Analysis of the mec-3 DNA sequence, which was obtained from genomic clones, indicates that there are alternative splicing patterns possible that could encode two full repeats of the motif in mec-3. A computer search of the National Biomedical Research Foundation Protein Sequence Database using the search program FASTP identified one copy of the motif in a cysteine-rich intestinal protein (CRIP) cloned from rat (Birkenmeier and Gordon, PNAS 83, 2516, 1986). We know of no other homeodomain-containing protein that contains a similar motif. The motif is similar but not identical to the pattern of cysteine and histidine residues in known metal-binding regions, but there is large variation among different classes of metal-binding proteins. Jeff Way previously noted the possibility that mec-3 might be a metal- binding protein because of the CxxC pattern of residues in the protein sequence (WBG 10:3, 32). Metal-binding regions can be sites for protein/protein interactions (including dimerization) or, in some proteins such as the zinc-finger containing proteins, metal-binding regions provide sites of contact with DNA. In either case, the region is of interest. If the metal-binding region is the site of a protein/protein interaction, it could be a region important in interacting with other components of the transcriptional machinery or it may play a role in the ability of the lin-11 protein to be localized to the correct cell type. If the potential metal-binding region is the site of nucleic acid contact, it could be binding to the same region of DNA as the homeodomain, to a separate region of the chromosome, or to RNA. We hope to test the functional importance of this region of lin-11.[See Figure 1]