InterPro domain: IPR002717

Histone acetyltransferases (HATs) fall into at least four different families based on sequence conservation within the HAT domain [ 1 ]. The MYST family is the largest family of HATs and is named after the founding members: MOZ, Ybf2/ Sas3, Sas2 and Tip60. MYST proteins mediate many biological functions including gene regulation, DNA repair, cell-cycle regulation and development [ 2 ] and have been shown to acetylate several non-histone substrates [ 3 ]. MYST proteins are autoregulated by posttranslational modifications [ 4 ].

The MYST-type HAT domain contains three regions: a central region associatedwith acetyl-CoA cofactor binding and catalysis in addition to flanking N- andC-terminal regions harboring respectively a C2HC-type zinc finger and a helix-turn-helix DNA-binding motif. The N- and C-terminal segmentsdirectly flanking the catalytic core are likely to play an important role inhistone substrate binding [ 5 , 6 ]. The catalytic mechanism for the MYST-type HAT domain is still unresolved but seems to involve a conserved glutamate that functions to abstract a proton from lysine to promote the nucleophilic attack on the acetyl carbonyl carbon of acetyl-CoA [ 7 , 7 , 8 , 8 ].

1. Histone modifying enzymes: structures, mechanisms, and specificities. Biochim. Biophys. Acta 1789, 58-68
2. MYST-family histone acetyltransferases: beyond chromatin. Cell. Mol. Life Sci. 68, 1147-56
3. Protein acetylation microarray reveals that NuA4 controls key metabolic target regulating gluconeogenesis. Cell 136, 1073-84
4. MYST protein acetyltransferase activity requires active site lysine autoacetylation. EMBO J. 31, 58-70
5. Crystal structure of yeast Esa1 suggests a unified mechanism for catalysis and substrate binding by histone acetyltransferases. Mol. Cell 6, 1195-205
6. The human monocytic leukemia zinc finger histone acetyltransferase domain contains DNA-binding activity implicated in chromatin targeting. J. Biol. Chem. 282, 36603-13
7. Autoacetylation of the MYST lysine acetyltransferase MOF protein. J. Biol. Chem. 287, 34917-26
8. Catalytic-site mutations in the MYST family histone Acetyltransferase Esa1. Genetics 178, 1209-20