Missense Variants Disrupt Polycomb Repression and Enable Ectopic Mesenchymal Lineage Conversion During Human Neural Differentiation.

Polycomb Repressive Complex 1 (PRC1) catalyzes H2AK119ub1 to facilitate transcriptional repression during development. dominant missense variants in , the principal E3 ligase of PRC1, are the genetic basis of Luo-Schoch-Yamamoto syndrome. To investigate the developmental impact of catalytically impaired RNF2 alleles, we engineered hESC lines harboring homozygous hypomorphic missense alleles ( ) that stably expresses RNF2 but results in reduced H2AK119ub1.