Coactivator condensation at super-enhancers links phase separation and gene control
- Sabari, B.
- Dall’Agnese, A.
- Boija, A.
- Klein, I.
- Coffey, E.
- Shrinivas, K.
- Abraham, B.
- Hannett, N.
- Zamudio, A.
- Manteiga, J.
- Li, C.
- Guo, Y.
- Day, D.
- Schuijers, J.
- Vasile, E.
- Malik, S.
- Hnisz, D.
- Lee, T.
- Cisse, I.
- Roeder, R.
- Sharp, P.
- Chakraborty, A.
- Young, R.
DOIAbstract
Super-enhancers (SEs) are clusters of enhancers that cooperatively assemble a high density of the transcriptional apparatus to drive robust expression of genes with prominent roles in cell identity. Here we demonstrate that the SE-enriched transcriptional coactivators BRD4 and MED1 form nuclear puncta at SEs that exhibit properties of liquid-like condensates and are disrupted by chemicals that perturb condensates. The intrinsically disordered regions (IDRs) of BRD4 and MED1 can form phase-separated droplets, and MED1-IDR droplets can compartmentalize and concentrate the transcription apparatus from nuclear extracts. These results support the idea that coactivators form phase-separated condensates at SEs that compartmentalize and concentrate...
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