Pair of unusual GCN5 histone acetyltransferases and ADA2 homologues in the protozoan parasite Toxoplasma gondii

Micah M. Bhatti, Meredith Livingston, Nandita Mullapudi, William Sullivan

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

GCN5 is a histone acetyltransferase (HAT) essential for development in mammals and critical to stress responses in yeast. The protozoan parasite Toxoplasma gondii is a serious opportunistic pathogen. The study of epigenetics and gene expression in this ancient eukaryote has pharmacological relevance and may facilitate the understanding of these processes in higher eukaryotes. Here we show that the disruption of T. gondii GCN5 yields viable parasites, which were subsequently employed in a proteomics study to identify gene products affected by its loss. Promoter analysis of these TgGCN5-dependcnt genes, which were mostly parasite specific, reveals a conserved T-rich element. The loss of TgGCN5 does not attenuate virulence in an in vivo mouse model. We also discovered that T. gondii is the only invertebrate reported to date possessing a second GCN5 (TgGCN5-B). TgGCN5-B harbors a strikingly divergent N-terminal domain required for nuclear localization. Despite high homology between the HAT domains, the two TgGCN5s exhibit differing substrate specificities. In contrast to TgGCN5-A, which exclusively targets lysine 18 of H3, TgGCN5-B acetylates multiple lysines in the H3 tail. We also identify two ADA2 homologues that interact differently with the TgGCN5s. TgGCN5-B has the potential to compensate for TgGCN5-A, which probably arose from a gene duplication unique to T. gondii. Our work reveals an unexpected complexity in the GCN5 machinery of this primitive eukaryote.

Original languageEnglish
Pages (from-to)62-76
Number of pages15
JournalEukaryotic Cell
Volume5
Issue number1
DOIs
StatePublished - Jan 2006

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Toxoplasma
Toxoplasma gondii
Protozoa
Parasites
Eukaryota
eukaryotic cells
Histone Acetyltransferases
parasites
Lysine
lysine
Gene Duplication
gene duplication
Invertebrates
substrate specificity
Substrate Specificity
Epigenomics
epigenetics
Proteomics
proteomics
Genes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Microbiology

Cite this

Pair of unusual GCN5 histone acetyltransferases and ADA2 homologues in the protozoan parasite Toxoplasma gondii. / Bhatti, Micah M.; Livingston, Meredith; Mullapudi, Nandita; Sullivan, William.

In: Eukaryotic Cell, Vol. 5, No. 1, 01.2006, p. 62-76.

Research output: Contribution to journalArticle

Bhatti, Micah M. ; Livingston, Meredith ; Mullapudi, Nandita ; Sullivan, William. / Pair of unusual GCN5 histone acetyltransferases and ADA2 homologues in the protozoan parasite Toxoplasma gondii. In: Eukaryotic Cell. 2006 ; Vol. 5, No. 1. pp. 62-76.
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