CD4+ Tregs drive post-ischemic sprouting angiogenesis via endothelial YY1/MAML1 reactivation [ChIP-seq]

We previously found that CD4+ regulatory T-cells (Tregs) are markedly reduced in type 2 diabetes (T2D) after ischemic injury in both mice and humans, and that Treg deficiency in immunodeficient mice impairs vascular regeneration. However, the mechanisms by which Tregs protect against diabetic vascular disease remain unclear.

Here, we demonstrate that endothelial cells (ECs) upregulate the transcription factor YY1 during post-ischemic vascular regeneration, but this response is blunted in diabetic ECs. Endothelial-specific deletion of YY1 leads to defective vascular regeneration following ischemia. Mechanistically, YY1 binds to the MAML1 promoter at regions enriched for H3K4me3 and H3K27ac.