biostudies-literatureSingh KDeutsche ForschungsgemeinschaftMinistry of Science, Research and the Arts Baden-Württemberg (MWK) and the German Research Foundation (DFG) throughe04920https://www.ebi.ac.uk/biostudies/studies/S-EPMC12697871biostudies-literatureUnknown12(46)Dysregulation of macrophage populations at the wound site is responsible for the non-healing state of chronic wounds. The underlying mechanisms in diabetic conditions at single cell resolution and therapeutic advances remain, however, largely unexplored. Here, it is reported that acetyl histone-H3 (Lys27), an epigenetic mark regulating the macrophage transcriptome, is lost in the hostile tissue microenvironment of diabetes. Diabetic conditions suppress the acetylation of histone, a critical regulator of trained immunity, by activating histone deacetylase (HDAC)-dependent deacetylation pathways. This, in consequence, suppresses STAT1 signaling in macrophages under diabetic conditions. Interestingly, butyrate, a potent HDAC inhibitor, restores the acetyl histone-H3 (Lys27)-dependent transcriAdvanced science (Weinheim, Baden-Wurttemberg, Germany)Restoring Histone Acetylation Accelerates Diabetic Wound Repair by Improving the Spatiotemporal Dynamics of Macrophages.PMC1269787135/1503-1 FUGG450627322251293561Pandey RKScharffetter-Kochanek KSingh KHainzl AWlaschek MHaas PWang YKrug LKoroma AKAghapour MMaity PCheng JfalseRestoring Histone Acetylation Accelerates Diabetic Wound Repair by Improving the Spatiotemporal Dynamics of Macrophages.Dysregulation of macrophage populations at the wound site is responsible for the non-healing state of chronic wounds. The underlying mechanisms in diabetic conditions at single cell resolution and therapeutic advances remain, however, largely unexplored. Here, it is reported that acetyl histone-H3 (Lys27), an epigenetic mark regulating the macrophage transcriptome, is lost in the hostile tissue microenvironment of diabetes. Diabetic conditions suppress the acetylation of histone, a critical regulator of trained immunity, by activating histone deacetylase (HDAC)-dependent deacetylation pathways. This, in consequence, suppresses STAT1 signaling in macrophages under diabetic conditions. Interestingly, butyrate, a potent HDAC inhibitor, restores the acetyl histone-H3 (Lys27)-dependent transcri2025-01-01T00:00:00Z2025 Dec2026-06-06T02:18:54.316Z2026-05-24T03:11:56.995ZS-EPMC126978714105135910.1002/advs.202504920