Hypoxia‐mediated regulation of DDX5 through decreased chromatin accessibility and post‐translational targeting restricts R‐loop accumulation

Solid tumors often experience local hypoxia, which is linked to aggressive disease and resistance to therapy. While most research on the biological response to hypoxia has focused on hypoxia-inducible genes, this study shows that chromatin accessibility is reduced in hypoxia, particularly at gene promoters, affecting specific pathways such as DNA repair, splicing, and the R-loop interactome. The study also found that DDX5, a gene encoding RNA helicase, is repressed in hypoxic conditions, leading to reduced R-loop accumulation. These findings suggest that the repression of multiple R-loop processing factors is a crucial part of the response to hypoxia, with each factor playing a specific and distinct role.