Components of the transcriptional machinery are selectively compartmentalized 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 Pol 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 disordered-mediated interactions can selectively compartmentalize functionally related protein from a complex mixture of proteins leading to regulation of a biochemical pathway.

Talk by:
Ben Sabari
UT Southwestern

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