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Induction and Monitoring of DNA Phase Separation in Living Cells by a Light-Switching Ruthenium Complex
- Source :
- Journal of the American Chemical Society. 143(30)
- Publication Year :
- 2021
-
Abstract
- Phase separation of DNA is involved in chromatin packing for the regulation of gene transcription. Visualization and manipulation of DNA phase separation in living cells present great challenges. Herein, we present a Ru(II) complex (Ru1) with high DNA binding affinity and DNA "light-switch" behavior that can induce and monitor DNA phase separation both in vitro and in living cells. Molecular dynamics simulations indicate that the two phen-PPh3 ligands with positively charged lipophilic triphenylphosphine substituents and flexible long alkyl chains in Ru1 play essential roles in the formation of multivalent binding forces between DNA molecules to induce DNA phase separation. Importantly, the unique environmental sensitive emission property of Ru1 enables direct visualization of the dynamic process of DNA phase separation in living cells by two-photon phosphorescent lifetime imaging. Moreover, Ru1 can change the gene expression pattern by modulating chromatin accessibility as demonstrated by integrating RNA-sequencing and transposase-accessible chromatin with high-throughput sequencing. In all, we present here the first small-molecule-based tracer and modulator of DNA phase separation in living cells and elucidate its impact on the chromatin state and transcriptome.
- Subjects :
- Light
chemistry.chemical_element
Molecular Dynamics Simulation
Ligands
Biochemistry
Catalysis
Ruthenium
Transcriptome
Molecular dynamics
chemistry.chemical_compound
Colloid and Surface Chemistry
Coordination Complexes
Gene expression
Molecule
Humans
Molecular Structure
Chemistry
General Chemistry
DNA
In vitro
Chromatin
A549 Cells
Biophysics
Subjects
Details
- ISSN :
- 15205126
- Volume :
- 143
- Issue :
- 30
- Database :
- OpenAIRE
- Journal :
- Journal of the American Chemical Society
- Accession number :
- edsair.doi.dedup.....13c35b25c9943c5a400d3be8f894248b