@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}
}
