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

XHXiaomei HeUniversity of California, Riverside JYJun YuanUniversity of California, Riverside LLLin LiUniversity of California, Riverside

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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