DDIT4 overexpression reshapes the histone modification landscape in human coronary artery smooth muscle cells: an H3K9ac and H3K27ac CUT&Tag study

This study investigates the epigenetic mechanisms by which DDIT4 promotes vascular smooth muscle cell (VSMC) dedifferentiation. We performed CUT&Tag sequencing for the active histone marks H3K9ac and H3K27ac in HCASMCs following DDIT4 overexpression. Our findings reveal that DDIT4, by inhibiting the pyruvate dehydrogenase complex, reduces acetyl-CoA levels and globally decreases histone acetylation. Specifically, we observe loss of H3K9ac and H3K27ac at the promoters of key contractile genes, providing an epigenetic explanation for the DDIT4-mediated suppression of the contractile phenotype and acceleration of atherosclerosis.