Polycomb group (PcG) proteins are crucial chromatin regulators during development. H2AK119ub1 (H2Aub) and H3K27me3 are catalyzed by Polycomb-repressive complex 1 and 2 (PRC1/2) respectively, and they largely overlap in the genome due to mutual recruitment of the two complexes. However, it is unclear whether PRC1/H2Aub and PRC2/H3K27me3 can also function independently. By developing an ultra-sensitive carrier-DNA-assisted chromatin immunoprecipitation sequencing method termed CATCH-Seq, we generated allelic H2Aub profiles in mouse gametes and early embryos. Our results revealed an unexpected genomewide decoupling of H2Aub and H3K27me3 in mouse preimplantation embryos, where H2Aub but not H3K27me3 was enriched at PcG targets while only H3K27me3 was deposited in the broad distal domains associated with DNA methylation-independent non-canonical imprinting. These observations suggest that H2Aub represses future bivalent genes during early embryogenesis without H3K27me3, but it is not required for the maintenance of non-canonical imprinting, which is mediated by maternal H3K27me3. Thus, our study reveals the distinct depositions and independent functions of H2Aub and H3K27me3 during early mammalian development.

多梳组 (PcG) 蛋白是发育过程中至关重要的染色质调节剂。H2AK119ub1 (H2Aub) 和 H3K27me3 分别由 Polycomb 抑制复合物 1 和 2 (PRC1/2) 催化，并且由于这两个复合物的相互募集，它们在基因组中大部分重叠。然而，目前尚不清楚 PRC1/H2Aub 和 PRC2/H3K27me3 是否也可以独立发挥作用。通过开发一种称为 CATCH-Seq 的超灵敏载体 DNA 辅助染色质免疫沉淀测序方法，我们在小鼠配子和早期胚胎中生成了等位基因 H2Aub 图谱。我们的结果揭示了小鼠植入前胚胎中 H2Aub 和 H3K27me3 的意外全基因组解偶联，其中 H2Aub 而不是 H3K27me3 在 PcG 目标处富集，而只有 H3K27me3 沉积在与 DNA 甲基化非依赖性非规范印记相关的广泛远端域中。这些观察结果表明，在没有 H3K27me3 的情况下，H2Aub 在早期胚胎发生期间抑制未来的二价基因，但它不是维持非规范印记所必需的，这是由母体 H3K27me3 介导的。因此，我们的研究揭示了 H2Aub 和 H3K27me3 在哺乳动物早期发育过程中的不同沉积和独立功能。