The nucleus is composed of functionally distinct membraneless compartments that undergo phase separation (PS). However, whether different subnuclear compartments are connected remains elusive. We identified a type of nuclear body with PS features composed of BAZ2A that associates with active chromatin. BAZ2A bodies depend on RNA transcription and BAZ2A non-disordered RNA-binding TAM domain. Although BAZ2A and H3K27me3 occupancies anticorrelate in the linear genome, in the nuclear space, BAZ2A bodies contact H3K27me3 bodies. BAZ2A-body disruption promotes BAZ2A invasion into H3K27me3 domains, causing H3K27me3-body loss and gene upregulation. Weak BAZ2A-RNA interactions, such as with nascent transcripts, promote BAZ2A bodies, whereas the strong binder long non-coding RNA (lncRNA) Malat1 impairs them while mediating BAZ2A association to chromatin at nuclear speckles. In addition to unraveling a direct connection between nuclear active and repressive compartments through PS mechanisms, the results also showed that the strength of RNA-protein interactions regulates this process, contributing to nuclear organization and the regulation of chromatin and gene expression.

细胞核由功能不同的无膜区室组成，这些区室经历相分离（PS）。然而，不同的亚核区室是否相连仍然难以捉摸。我们鉴定出一种具有 PS 特征的核体，由与活性染色质相关的 BAZ2A 组成。 BAZ2A 体依赖于 RNA 转录和 BAZ2A 无序 RNA 结合 TAM 结构域。尽管 BAZ2A 和 H3K27me3 占据在线性基因组中反相关，但在核空间中，BAZ2A 体与 H3K27me3 体接触。 BAZ2A-body 破坏促进 BAZ2A 侵入 H3K27me3 结构域，导致 H3K27me3-body 丢失和基因上调。弱的 BAZ2A-RNA 相互作用（例如与新生转录本的相互作用）会促进 BAZ2A 体，而强结合长非编码 RNA (lncRNA) Malat1会损害它们，同时介导 BAZ2A 与核斑点处染色质的关联。除了通过PS机制揭示核活性区室和抑制区室之间的直接联系外，结果还表明RNA-蛋白质相互作用的强度调节这一过程，有助于核组织以及染色质和基因表达的调节。