Unstructured transcription factor interactions enable emergent specificity
Summary
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 t
Content
# Unstructured transcription factor interactions enable emergent specificity
*Published: 2026 Mar 19*
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 Drosophila 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.
DOI: 10.1126/science.aeb6487