MYST family histone acetyltransferases in the protozoan parasite Toxoplasma gondii

Aaron T. Smith, Samantha D. Tucker-Samaras, Alan H. Fairlamb, William Sullivan

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

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 ∼3.5-kb transcript that can encode two proteins of 411 or 471 amino acids. TgMYST-B mRNA is ∼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.

Original languageEnglish
Pages (from-to)2057-2065
Number of pages9
JournalEukaryotic Cell
Volume4
Issue number12
DOIs
StatePublished - Dec 2005

Fingerprint

Histone Acetyltransferases
Toxoplasma
Toxoplasma gondii
histones
Histones
Protozoa
Parasites
parasites
chromatin
bradyzoites
Apicomplexa
tachyzoites
nucleosomes
Chromatin Assembly and Disassembly
Nucleosomes
zinc finger motif
Zinc Fingers
gene expression regulation
Gene Expression Regulation
Eukaryotic Cells

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Microbiology

Cite this

MYST family histone acetyltransferases in the protozoan parasite Toxoplasma gondii. / Smith, Aaron T.; Tucker-Samaras, Samantha D.; Fairlamb, Alan H.; Sullivan, William.

In: Eukaryotic Cell, Vol. 4, No. 12, 12.2005, p. 2057-2065.

Research output: Contribution to journalArticle

Smith, Aaron T. ; Tucker-Samaras, Samantha D. ; Fairlamb, Alan H. ; Sullivan, William. / MYST family histone acetyltransferases in the protozoan parasite Toxoplasma gondii. In: Eukaryotic Cell. 2005 ; Vol. 4, No. 12. pp. 2057-2065.
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