Zehender et al. recently demonstrated a novel mechanism for TGFβ-induced fibrosis in SSc, which involves a loss of epigenetic control over autophagy via a Smad3-dependent downregulation of the H4K16 histone acetyltransferase MYST1, mediating the activation of fibroblasts [29]. The gene discussed is TGFB1; the disease is systemic sclerosis.