The transcriptional co-activator and acetyltransferase p300 is required for fundamental cellular processes, including differentiation and growth. Here, we report that p300 forms phase separated condensates in the cell nucleus. The phase separation ability of p300 is regulated by autoacetylation and relies on its catalytic core components, including the histone acetyltransferase (HAT) domain, the autoinhibition loop, and bromodomain. p300 condensates sequester chromatin components, such as histone H3 tail and DNA, and are amplified through binding of p300 to the nucleosome. The catalytic HAT activity of p300 is decreased due to occlusion of the active site in the phase separated droplets, a large portion of which co-localizes with chromatin regions enriched in H3K27me3. Our findings suggest a model in which p300 condensates can act as a storage pool of the protein with reduced HAT activity, allowing p300 to be compartmentalized and concentrated at poised or repressed chromatin regions.

转录共激活因子和乙酰转移酶 p300 是基本细胞过程（包括分化和生长）所必需的。在这里，我们报告 p300 在细胞核中形成相分离的凝聚物。p300 的相分离能力受自乙酰化调节，并依赖于其催化核心成分，包括组蛋白乙酰转移酶 (HAT) 结构域、自抑制环和溴结构域。p300 缩合隔离染色质成分，例如组蛋白 H3 尾和 DNA，并通过 p300 与核小体的结合进行扩增。由于相分离液滴中的活性位点被封闭，p300 的催化 HAT 活性降低，其中大部分与富含 H3K27me3 的染色质区域共定位。