Journal
SCIENCE
Volume 361, Issue 6400, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aar2555
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Funding
- California Institute of Regenerative Medicine [LA1-08013]
- NIH [U01-EB021236, U54-DK107980]
- Howard Hughes Medical Institute
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Many eukaryotic transcription factors (TFs) contain intrinsically disordered low-complexity sequence domains (LCDs), but how these LCDs drive transactivation remains unclear. We used live-cell single-molecule imaging to reveal that TF LCDs form local high-concentration interaction hubs at synthetic and endogenous genomic loci.TF LCD hubs stabilize DNA binding, recruit RNA polymerase II (RNA Pol II), and activate transcription. LCD-LCD interactions within hubs are highly dynamic, display selectivity with binding partners, and are differentially sensitive to disruption by hexanediols. Under physiological conditions, rapid and reversible LCD-LCD interactions occur between TFs and the RNA Pol II machinery without detectable phase separation. Our findings reveal fundamental mechanisms underpinning transcriptional control and suggest a framework for developing single-molecule imaging screens for drugs targeting gene regulatory interactions implicated in disease.
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