Division of labor: different tasks for PRC1 and PRC2 in preimplantation embryos

Epigenetic regulation on gene expression is key to the decision and maintenance of cell fates during development.One of the old-est and the most explored epigenetic machinery involves the Poly-comb group (PcG) proteins,which regulate a plethora of critical biological processes,including chromatin organization,X chromo-some inactivation,proliferation and differentiation,and tumorige-nesis.The functions of PcG proteins are further diversified by the highly sophisticated multi-subunit complex assembly like LEGOs [1].Biochemically,PcG proteins assemble into two major complexes with unique chromatin-modifying activities:Polycomb repressive complex (PRC) 1 and PRC2.PRC1 contains a core involv-ing E3 ubiquitin ligases RING1A and RING1B,and catalyzes mono-ubiquitination on lysine 119 of histone H2A (H2AK119ub1),whereas PRC2 catalyzes mono-,di-,and tri-methylation on lysine 27 of histone H3 (H3K27me1/2/3).Although PRC1 and PRC2 coop-erate intimately in mediating transcriptional silencing,emerging evidence suggests independent roles at a subset of PcG targets.Recently,Zhu et al.[2] revealed distinct requirements for H2AK119ub1 and H3K27me3 to repress the expression of canoni-cal PcG targets and DNA methylation-independent non-canonical imprinting genes,respectively,during early embryonic development.