What question did this study set out to answer?

The aim is to uncover mechanisms by which YY1 interacts with R-loops to influence gene regulation.

March 13, 2026Journal of the American Chemical Society2 citations

YY1 Interacts with Promoter R-Loops to Regulate Transcription

Key Points

The aim is to uncover mechanisms by which YY1 interacts with R-loops to influence gene regulation.
Utilized APEX-based proximity labeling to analyze R-loop associated proteins.
Localized R-loops at specific genomic regions using a CRISPR-dCas9/gRNA system.
Integrated ChIP-seq and RNA-seq for comprehensive analysis of transcription regulation.
Identified YY1 as a novel protein that binds R-loops.
Demonstrated that enhanced R-loop formation increases YY1 occupancy at promoters.
Revealed that YY1-R-loop interactions broadly regulate transcription across various genes.

Abstract

R-loops play critical roles in gene regulation and genome stability. To elucidate the protein-mediated mechanisms governing R-loop dynamics, we leveraged APEX-based proximity labeling to profile the R-loop proximal proteome. By integrating the proteomic data, bioinformatic predictions, and biochemical characterizations, we identified YY1 as an R-loop-binding protein. Localized R-loop induction at specific genomic loci via a CRISPR-dCas9/gRNA targeting system enhanced the local YY1 occupancy. Furthermore, integrated ChIP-seq and RNA-seq analyses revealed that promoter-associated YY1-R-loop interactions broadly regulate transcription. Together, our work identifies YY1 as a novel R-loop interaction protein and establishes a role for this interaction in modulating gene expression.

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