The NuRD (Nucleosome Remodeling and histone Deacetylase) complex is thought to be involved in the negative control of gene expression during development through the establishment of repressive chromatin structures. In vertebrates, this complex comprises at least seven polypeptides, including the SWI2/SNF2 helicase/ATPase Mi-2, the histone deacetylases HDAC 1/2, the histone-binding proteins RbAp46/48 and the metastasis-associated proteins MTA 1/2. The developmental function of the NuRD complex is proposed to be achieved through association with sequence specific DNA-binding proteins that recruit it to chromosomal targets. Genes encoding NuRD components are widely conserved across animal and plant kingdoms. The genome of C. elegans encodes two Mi-2 orthologs, LET-418 and CHD-3 and mutations in their genes display distinct phenotypes.
let-418, but not
chd-3 is a class B synMuv gene (von Zelewsky et al., 2000). Furthermore,
let-418 is required for somatic differentiation during early embryonic development (Unhavaithaya et al., 2002) and acts as a co-repressor of LIN-1 to negatively regulate the Hox gene
lin-39 in the VPCs (Guerry et al., in press), whereas
chd-3 has no overt phenotype (von Zelewsky et al., 2000). Recently, however, it has been shown that mutations in
chd-3 (but not in
let-418) enhance defects in the pharyngeal specification of
pha-4 animals (Kiefer et al., 2006). By using standard biochemical techniques, such as co-immunoprecipitation, tandem affinity purification (TAP) and yeast two-hybrid screens, we found that CHD-3 and LET-418 form two distinct complexes with the C. elegans proteins HDA-1/HDAC, LIN-53/RbAp48 and EGR-1/MTA. Contrary to what has been proposed previously, neither of the two other class I histone deacetylases, HDA-2 or HDA-3, nor the second MTA ortholog EGL-27 or the second RbAp46 ortholog RBA-1 associated with LET-418 and CHD-3. Additionally, we found that the two worm Mi-2 orthologs interact, at least partially, with different factors. This is demonstrated, e.g., by the fact that only LET-418, but not CHD-3, associate with MEP-1, a zinc-finger protein required for the maintenance of somatic versus germline differentiation (Unhavaithaya et al., 2002). In agreement with these data, an expression analysis revealed that CHD-3 and LET-418 have different and only partially overlapping patterns throughout development. Altogether, our results suggest that the genome of C. elegans encodes two different NuRD-like complexes (one containing LET-418 and the other CHD-3) that fulfil different developmental functions. These results will be discussed.