Optical control of gene expression using a DNA G-quadruplex targeting reversible photoswitch

Area of Science:

• Chemical Biology
• Molecular Biology
• Genetics

Background:

• Transcriptional regulation is crucial for cellular activities.
• Small molecules offer ways to study gene expression but lack precise control.
• DNA G-quadruplexes (G4s) are key regulatory structures.

Purpose of the Study:

• To develop a light-controllable small molecule for precise transcriptional regulation.
• To investigate the spatiotemporal control of gene expression using a novel chemical tool.
• To demonstrate the application of G4switch in studying G4-associated cellular processes.

Main Methods:

• Development of G4switch, a cell-permeable, light-responsive G4 binder.
• In vitro biophysical characterization of light-mediated G4 binding.
• Cellular genomic mapping to identify G4switch binding sites in chromatin.
• Assays to assess light-dependent gene expression and cell proliferation.

Main Results:

• G4switch exhibits reversible, light-dependent binding to DNA G-quadruplexes.
• Genomic mapping confirmed G4-selective and light-controlled binding in cells.
• Spatiotemporal control over G4-containing gene expression was achieved.
• G4switch modulated G4-associated cell proliferation in a light-dependent manner.

Conclusions:

• G4switch is a novel chemical tool for precise, light-mediated control of gene expression.
• This approach allows interrogation of dynamic biological processes at the molecular level in cells.
• The study provides a new method for studying G4 structures and their roles in cellular functions.