The histone-chaperone LIN-53 (Rbbp4/7 in mammals) is part of several complexes such as PRC2, NuRD or Sin3 regulating chromatin modification and structure. Immunostaining reveals that LIN-53 is expressed virtually in all tissues of C. elegans (Lu, 1998; Seelk, unpublished). It was previously shown that
lin-53 functionally interacts with PRC2 in the germline in order to prevent reprogramming of germ cells (Patel et al. 2012; Seelk et al. 2016). However, it is unclear whether it has similar roles and functions in different cell types. Our ongoing study shows that LIN-53 interacts mainly with the Nucleosome remodeling and deacteylase (NuRD)-complex in C. elegans muscles. Staining of muscle proteins shows that lack of
lin-53 leads to a disruption of the muscle structure resulting in motility defects, which is phenocopied by depletion of members of the NuRD-complex. Muscle-specific interaction of LIN-53 with NuRD members was detected using mass-spec and interactions could be confirmed by Co-IPs. In contrast, while
lin-53 mutants have a shortened lifespan, NuRD mutants live normal or longer than control animals. This suggests that LIN-53 depletion has combinatorial effects possibly by affecting another chromatin regulating complex. Indeed, our work revealed that removal of the Histone deacetylase complex Sin3 affects lifespan similar to
lin-53 depletion. To identify affected gene expression due to lack of
lin-53 we carried out a transcriptome analysis. Muscle-specific genes but also the expression of genes, which are associated with both muscle maintenance and lifespan regulation are affected in
lin-53 mutants. Several small heat-shock proteins (sHSPs) were highly upregulated, among them
hsp-43 and
sip-1. RNAi against
hsp-43 in
lin-53 mutants suppressed the motility defects but not the short lifespan suggesting that de-repression of
hsp-43 contributes to the muscle defects. Besides a number of genes belonging to the oxidative stress pathway (e.g.
sknr-1, sod-genes) and metabolic enzymes (e.g.
tps-1) show decreased expression. We performed a metabolome analysis, which revealed that trehalose levels are significantly decreased in
lin-53 mutants. Feeding of trehalose indeed partially rescued the short lifespan of
lin-53 mutants. Additionally it was possible to show that
sknr-1 mutants live much shorter on
lin-53 RNAi. Our result that trehalose levels as well as oxidative stress genes are significantly decreased in
lin-53 mutants could explain the shortened lifespan of worms lacking
lin-53.