课题组研究人员使用近距离辅助光激活（PAPA），一种单分子蛋白质-蛋白质相互作用传感器，来研究IDR如何影响活细胞中TF相互作用以及与染色质的相互作用。课题组发现Sp1 DNA结合域（DBD）与染色质相互作用差，并且不与Sp1共定位。分离的IDR与全长Sp1的弱相互作用通过离子与各种不相关的DBD增强。果蝇多染色体的实时成像证实，IDR可以对非特异性的DBD赋予尖锐的位点特异性。这些发现表明，当多种非结构化相互作用的集合被瞬时DNA接触支架时，染色质上出现TF特异性。
据介绍，内在无序区（IDRs）如何影响染色质结合和转录因子（TFs）的核组织尚不清楚。
附：英文原文
Title: Unstructured transcription factor interactions enable emergent specificity
Author: Abrar A. Abidi, Claudia Cattoglio, Natalie N. Tang, Vinson B. Fan, Gina M. Dailey, Amir D. Hay, Prasanthi Kunamaneni, Daniel E. Milkie, Xavier Darzacq, Eric Betzig, Robert Tjian, Thomas G. W. Graham
Issue&Volume: 2026-03-19
Abstract: 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: aeb6487
Source: https://www.science.org/doi/10.1126/science.aeb6487