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Finally, a yeast ORF (ESA1 for essential SAS2-related acetyltransferase) was identified on the basis of its strong homology to MOF and Tip60. MOF was discovered in a genetic screen for gene products necessary for the hypertranscription and the acetylation of H4 at Lys-16 that is associated with Drosophila dosage compensation ( 18).

Tip60 was cloned due to its ability to interact with the viral transactivator HIV Tat in the two-hybrid system ( 11). MOZ was discovered due to its involvement in a chromosomal translocation that fuses this gene product in-frame with the transcriptional coactivator CBP, resulting in a form of acute myeloid leukemia ( 8). In addition to the effects on silencing of sas2 and sas3 mutants, other MYST family members are implicated in transcriptional control.

Therefore, without any biochemical evidence, it is not clear whether particular MYST family members are N α- or N ɛ-acetyltransferases. However, mutations in the amino-terminal acetyltransferases NAT1 and ARD1 also affect silencing of the mating type loci ( 17). Due to the relationships between transcriptional silencing and the acetylation of histones ( 14– 16), it is possible that SAS2 and SAS3 could be HATs, i.e., N ɛ-lysine acetyltransferases. Two of these proteins, Sas2p ( 9, 10) and Sas3p ( 9), are apparently involved in the control of transcriptional silencing in yeast. One of these, Tip60, was recently shown to acetylate histone substrates ( 13). Members of a recently discovered group of proteins, known as the MYST family ( 7, 8) for its founding members MOZ ( 8), YBF2/SAS3 ( 9), SAS2 ( 9, 10), Tip60 ( 11), have a subset of the motifs that characterize the GNAT superfamily ( 7, 12).

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Although Hat1p and Gcn5p have different substrate specificities ( 3), they share a series of motifs with the superfamily of N-acetyltransferases (referred to as GNAT for GCN5-related N-acetyltransferases), a group that includes several amino-terminal acetyltransferases ( 7). The first two histone acetyltransferases (HATs) to be cloned and characterized were the deposition-related HAT1 ( 5) from yeast and the transcription-related HAT from Tetrahymena, p55, that was highly similar to yeast Gcn5p ( 6).

Hypertranscribe review