YY1 Interacts with Promoter R-Loops to Regulate Transcription

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.