Imaging dynamic and selective low-complexity domain interactions that control gene transcription

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• Eukaryotic transcription factors (TFs) often possess intrinsically disordered low-complexity sequence domains (LCDs).
• The precise role of these LCDs in driving transcriptional activation is not fully understood.

Purpose of the Study:

• To elucidate the mechanisms by which TF LCDs contribute to transcriptional activation.
• To investigate the in vivo behavior of TF LCDs at genomic loci.

Main Methods:

• Live-cell single-molecule imaging was employed to observe TF LCDs.
• The study utilized both synthetic and endogenous genomic loci for observation.
• Interactions were analyzed for dynamics, selectivity, and sensitivity to hexanediols.

Main Results:

• TF LCDs form local, high-concentration interaction hubs at genomic sites.
• These hubs stabilize DNA binding, recruit RNA Polymerase II (RNA Pol II), and activate transcription.
• LCD-LCD interactions are dynamic, selective, and reversible, occurring without phase separation under physiological conditions.

Conclusions:

• TF LCDs are critical for transcriptional control by forming dynamic interaction hubs.
• These hubs facilitate stable DNA binding and efficient recruitment of RNA Pol II.
• The findings provide a framework for developing drug screens targeting gene regulation.