@article {70329,
	title = {Unstructured transcription factor interactions enable emergent specificity.},
	journal = {Science},
	year = {2026},
	month = {2026 Mar 19},
	pages = {eaeb6487},
	abstract = {<p>How intrinsically disordered regions (IDRs) influence chromatin binding and nuclear organization of transcription factors (TFs) remains unclear. We employed proximity-assisted photoactivation (PAPA), a single-molecule protein-protein interaction sensor, to investigate how IDRs might influence TF interactions with each other and with chromatin in live cells. We found that the Sp1 DNA binding domain (DBD) interacted poorly with chromatin and did not colocalize with Sp1. Weak interaction of the isolated IDR with full-length Sp1 was enhanced by fusion to various unrelated DBDs. Live imaging of polytene chromosomes confirmed that an IDR could confer sharp locus specificity on an otherwise nonspecific DBD. These findings suggest that TF specificity emerges on chromatin when ensembles of diverse, unstructured interactions are scaffolded by transient DNA contacts.</p>
},
	issn = {1095-9203},
	doi = {10.1126/science.aeb6487},
	url = {https://doi.org/10.1126/science.aeb6487},
	author = {Abidi, Abrar A and Cattoglio, Claudia and Tang, Natalie N and Fan, Vinson B and Dailey, Gina M and Hay, Amir D and Kunamaneni, Prasanthi and Milkie, Daniel E and Darzacq, Xavier and Betzig, Eric and Tjian, Robert and Graham, Thomas G W}
}
@article {49293,
	title = {Imaging dynamic and selective low-complexity domain interactions that control gene transcription.},
	journal = {Science (New York, N.Y.)},
	volume = {361},
	year = {2018},
	month = {2018 Jun 21},
	pages = {eaar2555},
	abstract = {<p>Many eukaryotic transcription factors (TFs) contain intrinsically disordered low-complexity domains (LCDs), but how they drive transactivation remains unclear. Here, live-cell single-molecule imaging reveals 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 (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 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 novel drugs targeting gene regulatory interactions implicated in disease.</p>
},
	issn = {1095-9203},
	doi = {10.1126/science.aar2555},
	author = {Chong, Shasha and Dugast-Darzacq, Claire and Liu, Zhe and Dong, Peng and Dailey, Gina M and Cattoglio, Claudia and Heckert, Alec and Banala, Sambashiva and Lavis, Luke and Darzacq, Xavier and Tjian, Robert}
}
