Inactivation of H3K9m3 methyltransferase SETDB1 and zinc finger protein ZNF274 results in reactivation of SNRPN and SNORD116 cluster from the maternal chromosomes in PWS patient iPSCs and iPSC-derived neurons, respectively.
This suggests that the ZNF274 complex is a separate imprinting mark that represses maternal PWS gene expression in neurons and is a potential target for future therapeutic applications to rescue the PWS phenotype.
This observation suggests that the ZNF274/SETDB1 complex bound to the SNORD116 cluster may protect the PWS-IC from DNA demethylation during early development.