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

Nehmé Saksouk, Micah M. Bhatti, Sylvie Kieffer, Aaron T. Smith, Karine Musset, Jérôme Garin, William Sullivan, Marie France Cesbron-Delauw, Mohamed Ali Hakimi

Research output: Contribution to journalArticle

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Abstract

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 [K8] 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.

Original languageEnglish
Pages (from-to)10301-10314
Number of pages14
JournalMolecular and Cellular Biology
Volume25
Issue number23
DOIs
StatePublished - Dec 2005

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Toxoplasma
Histones
Parasites
Gene Expression
Histone Deacetylases
Life Cycle Stages
Eukaryota
Epigenomics
Histone Code
Plasmodium malariae
Acetylesterase
Chromatin Assembly and Disassembly
Eukaryotic Cells
Acetylation
Methylation
Transcriptional Activation
Arginine
Transcription Factors

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Histone-modifying complexes regulate gene expression pertinent to the differentiation of the protozoan parasite Toxoplasma gondii. / Saksouk, Nehmé; Bhatti, Micah M.; Kieffer, Sylvie; Smith, Aaron T.; Musset, Karine; Garin, Jérôme; Sullivan, William; Cesbron-Delauw, Marie France; Hakimi, Mohamed Ali.

In: Molecular and Cellular Biology, Vol. 25, No. 23, 12.2005, p. 10301-10314.

Research output: Contribution to journalArticle

Saksouk, Nehmé ; Bhatti, Micah M. ; Kieffer, Sylvie ; Smith, Aaron T. ; Musset, Karine ; Garin, Jérôme ; Sullivan, William ; Cesbron-Delauw, Marie France ; Hakimi, Mohamed Ali. / Histone-modifying complexes regulate gene expression pertinent to the differentiation of the protozoan parasite Toxoplasma gondii. In: Molecular and Cellular Biology. 2005 ; Vol. 25, No. 23. pp. 10301-10314.
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