Functional Partitioning of Transcriptional Regulators by Patterned Charge Blocks

Lyons, H. et al. Functional partitioning of transcriptional regulators by patterned charge blocks. Cell 186, (2023). DOI: 10.1016/j.cell.2022.12.013

Researchers from UTSW Medical Center discovered that the charge patterning in intrinsically disordered regions (IDRs) of transcriptional regulators mediate selective partitioning, which has functional consequences for gene activation. Lyons et al. focused on the protein MED1, which forms part of the transcriptional machinery critical for gene regulation. MED1 has a large IDR known to compose part of some biomolecular condensates. The researchers exploited this property and exposed MED1 to human nuclear extracts to isolate MED1 condensates and determined the components that harbor inside and/or outside the condensates.

Analytical results show that positive transcriptional regulators are enriched in MED1 condensates, and the negative regulators are excluded out. Further investigations show that charge patterning in IDR dictates this selective partitioning. Researchers demonstrate by removing or adding IDRs, they can control the proteins included in the condensates, which has functional consequences. These findings may provide a new approach to control gene regulation and a tool to tackle various diseases.

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