The Polycomb repressive complex 2 (PRC2) is an essential epigenetic regulator that deposits repressive H3K27me3. PRC2 subunits form two holocomplexes—PRC2.1 and PRC2.2—but the roles of these two PRC2 assemblies during differentiation are unclear. We employed auxin-inducible degradation to deplete PRC2.1 subunit MTF2 or PRC2.2 subunit JARID2 during differentiation of embryonic stem cells (ESCs) to neural progenitors (NPCs). Depletion of either MTF2 or JARID2 resulted in incomplete differentiation due to defects in gene regulation. Distinct sets of Polycomb target genes were derepressed in the absence of MTF2 or JARID2. MTF2-sensitive genes were marked by H3K27me3 in ESCs and remained silent during differentiation, whereas JARID2-sensitive genes were preferentially active in ESCs and became newly repressed in NPCs. Thus, MTF2 and JARID2 contribute non-redundantly to Polycomb silencing, suggesting that PRC2.1 and PRC2.2 have distinct functions in maintaining and establishing, respectively, Polycomb repression during differentiation.

Polycomb抑制复合物 2 (PRC2) 是一种重要的表观遗传调节因子，可沉积抑制性 H3K27me3。 PRC2 亚基形成两个全复合体——PRC2.1 和 PRC2.2——但这两个 PRC2 组件在分化过程中的作用尚不清楚。我们在胚胎干细胞（ESC）分化为神经祖细胞（NPC）期间采用生长素诱导降解来消耗 PRC2.1 亚基 MTF2 或 PRC2.2 亚基 JARID2。由于基因调控缺陷，MTF2 或 JARID2 的缺失会导致分化不完全。在没有 MTF2 或 JARID2 的情况下，不同的Polycomb靶基因组被去抑制。 MTF2敏感基因在ESC中被H3K27me3标记，并在分化过程中保持沉默，而JARID2敏感基因在ESC中优先活跃，并在NPC中新被抑制。因此，MTF2和JARID2对Polycomb沉默有非冗余的贡献，表明PRC2.1和PRC2.2分别在维持和建立分化过程中的Polycomb抑制方面具有不同的功能。