Data from: Multi-omic analyses identify molecular targets of Chd7 that mediate CHARGE syndrome model phenotypes

CHARGE syndrome is a developmental disorder that affects 1 in 10,000
births, and patients exhibit both physical and behavioral characteristics.
De novo mutations in chd7 (chromodomain helicase DNA binding protein 7)
cause 67% of CHARGE syndrome cases. Chd7 is a DNA-binding chromatin
remodeler with thousands of predicted binding sites in the genome, making
it challenging to define molecular pathways linking loss of chd7 to CHARGE
phenotypes. To address this problem, here we used a previously
characterized zebrafish CHARGE model to generate transcriptomic and
proteomic datasets from larval zebrafish head tissue at two developmental
time points. By integrating these datasets with differential expression,
pathway, and upstream regulator analyses, we identified multiple
consistently dysregulated pathways and defined a set of candidate genes
that link loss of chd7 with disease-related phenotypes. Finally, to
functionally validate the roles of these genes, CRISPR/Cas9-mediated
knockdown of capgb, nefla, or rdh5 phenocopies behavioral defects seen in
chd7 mutants. Our data provide a resource for further investigation of
molecular mediators of chd7 and a template to reveal functionally relevant
therapeutic targets to alleviate specific aspects of CHARGE syndrome.