Components of transcriptional machinery are selectively partitioned into specific condensates, often mediated by protein disorder, yet we know little about how this specificity is achieved. Here, we show that condensates composed of the intrinsically disordered region (IDR) of MED1 selectively partition RNA polymerase II together with its positive allosteric regulators while excluding negative regulators. This selective compartmentalization is sufficient to activate transcription and is required for gene activation during a cell-state transition. The IDRs of partitioned proteins are necessary and sufficient for selective compartmentalization and require alternating blocks of charged amino acids. Disrupting this charge pattern prevents partitioning, whereas adding the pattern to proteins promotes partitioning with functional consequences for gene activation. IDRs with similar patterned charge blocks show similar partitioning and function. These findings demonstrate that disorder-mediated interactions can selectively compartmentalize specific functionally related proteins from a complex mixture of biomolecules, leading to regulation of a biochemical pathway.

转录机器的组成部分被选择性地分成特定的缩合物，通常由蛋白质紊乱介导，但我们对如何实现这种特异性知之甚少。在这里，我们发现由 MED1 的本质无序区域 (IDR) 组成的缩合物选择性地将 RNA 聚合酶 II 及其正变构调节剂分开，同时排除负调节剂。这种选择性区室化足以激活转录，并且是细胞状态转变期间基因激活所必需的。分区蛋白质的 IDR 对于选择性区室化是必要且充分的，并且需要交替的带电氨基酸块。破坏这种电荷模式可以防止分区，而将这种模式添加到蛋白质中可以促进分区，从而对基因激活产生功能性影响。具有相似图案电荷块的 IDR 表现出相似的分区和功能。这些发现表明，疾病介导的相互作用可以选择性地将特定功能相关的蛋白质从复杂的生物分子混合物中分离出来，从而调节生化途径。