The restructuring of chromatin precedes tightly regulated events such as DNA 
transcription, replication, and repair. One type of chromatin remodeling 
involves the covalent modification of nucleosomes by histone acetyltransferase 
(HAT) complexes. The observation that apicidin exerts antiprotozoal activity by 
targeting a histone deacetyltransferase has prompted our search for more 
components of the histone modifying machinery in parasitic protozoa. We have 
previously identified GNAT family HATs in the opportunistic pathogen Toxoplasma 
gondii and now describe the first MYST (named for members MOZ, Ybf2/Sas3, Sas2, 
and Tip60) family HATs in apicomplexa (TgMYST-A and -B). The TgMYST-A genomic 
locus is singular and generates a approximately 3.5-kb transcript that can 
encode two proteins of 411 or 471 amino acids. TgMYST-B mRNA is approximately 
7.0 kb and encodes a second MYST homologue. In addition to the canonical MYST 
HAT catalytic domain, both TgMYST-A and -B possess an atypical C2HC zinc finger 
and a chromodomain. Recombinant TgMYST-A exhibits a predilection to acetylate 
histone H4 in vitro at lysines 5, 8, 12, and 16. Antibody generated to TgMYST-A 
reveals that both the long and short (predominant) versions are present in the 
nucleus and are also plentiful in the cytoplasm. Moreover, both TgMYST-A forms 
are far more abundant in rapidly replicating parasites (tachyzoites) than 
encysted parasites (bradyzoites). A bioinformatics survey of the Toxoplasma 
genome reveals numerous homologues known to operate in native MYST complexes. 
The characterization of TgMYST HATs represents another important step toward 
understanding the regulation of gene expression in pathogenic protozoa and 
provides evolutionary insight into how these processes operate in eukaryotic 
cells in general.