ApiLoc - A database of published protein sub-cellular localisation in Apicomplexa

version 3 (curated until May 28, 2011)

Histone-modifying complexes regulate gene expression pertinent to the differentiation of the protozoan parasite Toxoplasma gondii.

Saksouk, N., Bhatti, M. M., Kieffer, S., Smith, A. T., Musset, K., Garin, J., Sullivan, W. J. Jr, Cesbron-Delauw, M. F., Hakimi, M. A. (2005 Dec, Mol Cell Biol)

Pathogenic apicomplexan parasites like Toxoplasma and Plasmodium (malaria) have complex life cycles consisting of multiple stages. The ability to differentiate from one stage to another requires dramatic transcriptional changes, yet there is a paucity of transcription factors in these protozoa. In contrast, we show here that Toxoplasma possesses extensive chromatin remodeling machinery that modulates gene expression relevant to differentiation. We find that, as in other eukaryotes, histone acetylation and arginine methylation are marks of gene activation in Toxoplasma. We have identified mediators of these histone modifications, as well as a histone deacetylase (HDAC), and correlate their presence at target promoters in a stage-specific manner. We purified the first HDAC complex from apicomplexans, which contains novel components in addition to others previously reported in eukaryotes. A Toxoplasma orthologue of the arginine methyltransferase CARM1 appears to work in concert with the acetylase TgGCN5, which exhibits an unusual bias for H3 [K18] in vitro. Inhibition of TgCARM1 induces differentiation, showing that the parasite life cycle can be manipulated by interfering with epigenetic machinery. This may lead to new approaches for therapy against protozoal diseases and highlights Toxoplasma as an informative model to study the evolution of epigenetics in eukaryotic cells.

PubMed: 16287846, full text

Localisation information

TGME49_027290 (HDAC3) histone deacetylase, putative

Experimental localisation: nucleus during intracellular tachyzoite, not nucleolus during intracellular tachyzoite
  • Species: Toxoplasma gondii
  • Quote inferring localisation: "Whereas some class I- and class II-related enzymes were predominantly cytoplasmic (data not shown), TgHDAC3 (class I) was exclusively localized in the parasite nucleus, being largely excluded from the nucleolus, as observed for acetylated H4 (Fig. 2A)"
  • Microscopy type: Light
  • Microscopy method: HA tag
  • Strain: RH
  • Gene model mapping comments: blast from DQ004745.1, annotation matches
  • Localisation record: nucleus and not nucleolus during intracellular tachyzoites

TGME49_109140 (TBL1) transducin beta-like protein 1 (TgTBL1)

Experimental localisation: nucleus during tachyzoite, not nucleolus during tachyzoite
  • Species: Toxoplasma gondii
  • Quote inferring localisation: "This protein ectopically expressed in tachyzoites localizes exclusively in the nucleus and is also excluded from the nucleolus, as observed previously for TgHDAC3"
  • Microscopy type: Light
  • Microscopy method: HA tag
  • Strain: RH
  • Gene model mapping comments: blast from DQ004746.1, annotation matches
  • Localisation record: nucleus and not nucleolus during tachyzoite

TGME49_061240 (H3) histone H3

Experimental localisation: nucleus during intracellular tachyzoite
  • Species: Toxoplasma gondii
  • Quote inferring localisation: "We detected methylation of H3 [R17] within tachyzoite nuclei by using immunofluorescent staining (Fig. 5A)."
  • Microscopy type: Light
  • Microscopy method: antibody to homologue
  • Strain: RH
  • Gene model mapping comments: blast from XP_002365267.1, annotation matches
  • Localisation record: nucleus during intracellular tachyzoite

TGME49_094270 (CARM1) arginine methyltransferase protein, putative

Experimental localisation: nucleus during tachyzoite
  • Species: Toxoplasma gondii
  • Quote inferring localisation: "Ectopically expressed HA-FLAG-TgCARM1 is able to localize to the parasite nucleus, consistent with a role in transcriptional regulation"
  • Microscopy type: Light
  • Microscopy method: polyclonal antibody directly to protein
  • Strain: RH
  • Gene model mapping comments: Blast from AY820755.1, annotation matches
  • Localisation record: nucleus during tachyzoite