TBX1 and 22q11.2 deletion syndrome: T-box proteins, mutated in Holt-Oram syndrome (TBX5) and DiGeorge syndrome (TBX1), display highly conserved residues, allowing direct interaction with both histone demethylase (H3K27) and methyltransferase (H3K4): both syndromes include cardiac manifestations [24], underlining the highly regulatory nature of these pathogenic mechanisms; treatment with demethylase inhibitors of Tbx1-KO mice rescues the cardiac phenotype [25].