National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
University of the Chinese Academy of Sciences, Beijing, China.
Nat Cell Biol. 2020 Apr;22(4):439-452. doi: 10.1038/s41556-020-0484-1. Epub 2020 Mar 23.
Stable propagation of epigenetic information is important for maintaining cell identity in multicellular organisms. However, it remains largely unknown how mono-ubiquitinated histone H2A on lysine 119 (H2AK119ub1) is established and stably propagated during cell division. In this study, we found that the proteins RYBP and YAF2 each specifically bind H2AK119ub1 to recruit the RYBP-PRC1 or YAF2-PRC1 complex to catalyse the ubiquitination of H2A on neighbouring nucleosomes through a positive-feedback model. Additionally, we demonstrated that histone H1-compacted chromatin enhances the distal propagation of H2AK119ub1, thereby reinforcing the inheritance of H2AK119ub1 during cell division. Moreover, we showed that either disruption of RYBP/YAF2-PRC1 activity or impairment of histone H1-dependent chromatin compaction resulted in a significant defect of the maintenance of H2AK119ub1. Therefore, our results suggest that histone H1-dependent chromatin compaction plays a critical role in the stable propagation of H2AK119ub1 by RYBP/YAF2-PRC1 during cell division.
组蛋白 H2A 第 119 位赖氨酸单泛素化（H2AK119ub1）在细胞分裂过程中的建立和稳定传递如何实现仍然知之甚少。在这项研究中，我们发现 RYBP 和 YAF2 蛋白各自特异性地结合 H2AK119ub1，招募 RYBP-PRC1 或 YAF2-PRC1 复合物，通过正反馈模型催化邻近核小体上 H2A 的泛素化。此外，我们证明组蛋白 H1 压缩染色质增强了 H2AK119ub1 的远程传递，从而在细胞分裂过程中加强了 H2AK119ub1 的遗传。此外，我们表明，无论是 RYBP/YAF2-PRC1 活性的破坏还是组蛋白 H1 依赖性染色质压缩的损害，都会导致 H2AK119ub1 的维持出现显著缺陷。因此，我们的研究结果表明，在细胞分裂过程中，组蛋白 H1 依赖性染色质压缩通过 RYBP/YAF2-PRC1 在 H2AK119ub1 的稳定传递中发挥关键作用。
