YY1 interacts with guanine quadruplexes to regulate DNA looping and gene expression

Area of Science:

• Molecular Biology
• Genetics
• Epigenetics

Background:

• DNA guanine quadruplexes (G4) are critical structures involved in DNA replication, transcription, and genome stability.
• The transcription factor Yin and Yang 1 (YY1) is known to play roles in various cellular processes.

Purpose of the Study:

• To investigate the direct interaction between YY1 and G4 structures.
• To elucidate the role of YY1-G4 binding in DNA looping and gene expression.

Main Methods:

• Chromatin immunoprecipitation sequencing (ChIP-seq) to identify YY1 binding sites.
• Analysis of YY1 binding site overlap with G4 structure loci.
• Assays to assess the impact of YY1 dimerization and G4 binding on DNA looping.
• Treatment with G4-stabilizing ligands to study gene expression modulation.

Main Results:

• YY1 directly binds to G4 structures.
• YY1 binding sites extensively overlap with G4 loci in chromatin.
• YY1 dimerization and G4 binding are essential for YY1-mediated long-range DNA looping.
• Disruption of YY1-G4 interaction significantly impairs DNA looping.
• G4-stabilizing ligands affect the expression of genes associated with both proximal and distal G4 structures.

Conclusions:

• YY1 is identified as a DNA G4-binding protein.
• YY1-mediated long-range DNA looping depends on YY1 dimerization and its recognition of G4 structures.
• The YY1-G4 interaction plays a significant role in regulating gene expression through chromatin looping.