The NuRD (nucleosome remodeling and histone deacetylase) complex is thought to be involved in the establishment of a repressive chromatin structure and in the negative control of gene expression. In vertebrates, this complex comprises at least seven polypeptides, including the SWI2/SNF2 helicase/ATPase Mi-2, the histone deacetylases HDAC1/2, the histone-binding proteins RbAp46/48, the metastasis-associated proteins MTA1/2, the methyl-CpG binding protein MBD3 and the potent transcriptional repressor
p66. Orthologues of these NuRD subunits are also encoded by the genome of C.elegans, among them the two Mi-2 homologues, LET-418 and CHD-3.
let-418 mutants show pleiotropic phenotypes, among them sterility and larval arrest (von Zelewsky et al., 2000). In contrast,
chd-3 mutants exhibit no phenotype. However,
chd-3 null mutants enhance the Let-418 phenotype. This suggests that the two proteins have partially redundant functions during development (von Zelewsky et al., 2000). Our data suggest that LET-418 and CHD-3 may not be interchangeable members of the same complex, but rather are part of different NuRD or NuRD-like complexes. To find proteins interacting with LET-418 and CHD-3 and to characterize putative NuRD complexes in C.elegans, we take different approaches. We use standard biochemical techniques, like co-immunoprecipitation, TAP method, yeast two-hybrid experiments, and we started a synthetic lethal genetic screen using the
chd-3(
eh4) strain. von Zelewsky et al., Development 127: 5277-5284 (2000).