Chromatin is a dynamic structure which is condensed or relaxed to allow tissue specific expression of developmental genes. Mi2 proteins are among conserved ATP-dependent enzymes that shape chromatin during development. In Caenorhabditis elegans the Mi2 homolog, LET-418, operates during developmental processes such as germ cell fate maintenance, blast cell proliferation and differentiation and vulval development. To better understand the role of LET-418 chromatin remodeler, we analysed its transcriptional output at different life stages of C. elegans: embryo, L1 larvae and young adult. Other than an increase in the number of deregulated genes through the progression of the life cycle, a unique tissue enrichment signature was observed for each life stage. In addition, we found that a subset of upregulated genes at L1 and adult stage were organised in clusters. Most of these gene including pals, math, clec and fbxa gene families are involved in proteostasis and immune response. Using qRT-PCR we validated the upregulation of a subset of these genes, as well as additional genes located in the clusters. These results suggest that LET-418 may act globally on chromatin domains that contain transcriptionally co-regulated genes. To determine if LET-418 is binding directly to these chromatin regions, we are currently performing DamID profiling experiments, which rely on the expression of LET-418 fused to the E. coli methylase in the worm. Furthermore, to test if the genome localisation of these LET-418 regulated genes is essential, we are generating transgenic strains expressing representative genes from a different region of the chromosome. Altogether, these results will allow us to determine whether LET-418 is regulating these gene clusters as a chromatin domain located at a specific locus in the genome. Finally, to know whether this chromatin-based regulation of immune response genes is relevant to the pathogen response, we will test whether
let-418 mutants are more resistant to pathogens.