RBBP6 orchestrates diabetic endothelial dysfunction viadisrupting JUNB-centric chromatin topology

This dysfunction is characterized by impaired endothelial nitric oxide synthase (eNOS) activity, reduced nitric oxide (NO) production, and diminished angiogenic capacity, ultimately contributing to tissue ischemia and complications such as diabetic nephropathy, coronary artery disease, and peripheral arterial disease.

These complications significantly increase morbidity and mortality in diabetic patients. Endothelial cells, which regulate vascular development and function, rely on the coordinated activity of cis-regulatory elements, including enhancers and promoters, which are influenced by the three-dimensional (3D) genome architecture and transcription factors (TFs) such as AP-1, ETS, and GATA families. However, the mechanisms by which these TFs mediate enhancer-promoter interactions and how these interactions are altered under diabetic conditions remain poorly understood.