Functional partitioning of transcriptional regulators by patterned charge blocks

Heankel Lyons, Reshma T. Veettil, Prashant Pradhan, Christy Fornero, Nancy De La Cruz, Keiichi Ito, Mikayla Eppert, Robert G. Roeder, Benjamin R. Sabari

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)327-345.e28
Issue number2
StatePublished - Jan 19 2023


  • biomolecular condensates
  • functional compartmentalization
  • gene activation
  • nuclear organization
  • phase separation
  • protein disorder
  • selective partitioning
  • transcription

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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