Cloning and analysis of a Toxoplasma gondii histone acetyltransferase: a novel chromatin remodelling factor in Apicomplexan parasites

Hettmann, Christine; Soldati, Dominique

doi:10.1093/nar/27.22.4344

Cited by 31 publications

(21 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Histone acetylation activities like those described above are mediated by HATs and HDACs. A GCN5 family HAT has been described in Toxoplasma (27,53), but no one has characterized an HDAC enzyme in this parasite. Bioinformatic analysis of the Toxoplasma genome (http://ToxoDB.org) (33) reveals a family of six putative HDACs in Toxoplasma, which can be grouped into three classes (I, II, and III) based upon similarity to human homologues (data not shown; 13, 23).…”

Section: Resultsmentioning

confidence: 99%

Histone-Modifying Complexes Regulate Gene Expression Pertinent to the Differentiation of the Protozoan Parasite Toxoplasma gondii

Saksouk¹,

Bhatti

Kieffer

et al. 2005

Molecular and Cellular Biology

179

257

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

confidence: 99%

Histone-Modifying Complexes Regulate Gene Expression Pertinent to the Differentiation of the Protozoan Parasite Toxoplasma gondii

Saksouk¹,

Bhatti

Kieffer

et al. 2005

Molecular and Cellular Biology

179

257

View full text Add to dashboard Cite

show abstract

“…Subsequent protein sequencing revealed that it was a homolog of Saccharomyces cerevisiae (yeast) Gcn5 (77), previously identified as a transcriptional adaptor (or coactivator) involved in the interaction between certain activators and the transcription complex (17,154,213). Homologs of Gcn5 have more recently been cloned and sequenced from numerous divergent organisms-such as human (36), mouse (276), Schizosaccharomyces pombe, Drosophila melanogaster (215), Arabidopsis thalania, and Toxoplasma gondii (102)-suggesting that its function is highly conserved throughout the eukaryotes.…”

Section: Gnat Superfamilymentioning

confidence: 99%

Acetylation of Histones and Transcription-Related Factors

Sterner

Berger

2000

Microbiol Mol Biol Rev

1,550

1,294

View full text Add to dashboard Cite

SUMMARY The state of chromatin (the packaging of DNA in eukaryotes) has long been recognized to have major effects on levels of gene expression, and numerous chromatin-altering strategies—including ATP-dependent remodeling and histone modification—are employed in the cell to bring about transcriptional regulation. Of these, histone acetylation is one of the best characterized, as recent years have seen the identification and further study of many histone acetyltransferase (HAT) proteins and their associated complexes. Interestingly, most of these proteins were previously shown to have coactivator or other transcription-related functions. Confirmed and putative HAT proteins have been identified from various organisms from yeast to humans, and they include Gcn5-related N-acetyltransferase (GNAT) superfamily members Gcn5, PCAF, Elp3, Hpa2, and Hat1: MYST proteins Sas2, Sas3, Esa1, MOF, Tip60, MOZ, MORF, and HBO1; global coactivators p300 and CREB-binding protein; nuclear receptor coactivators SRC-1, ACTR, and TIF2; TATA-binding protein-associated factor TAFII250 and its homologs; and subunits of RNA polymerase III general factor TFIIIC. The acetylation and transcriptional functions of these HATs and the native complexes containing them (such as yeast SAGA, NuA4, and possibly analogous human complexes) are discussed. In addition, some of these HATs are also known to modify certain nonhistone transcription-related proteins, including high-mobility-group chromatin proteins, activators such as p53, coactivators, and general factors. Thus, we also detail these known factor acetyltransferase (FAT) substrates and the demonstrated or potential roles of their acetylation in transcriptional processes.

show abstract

“…However, CBP-or CREB-like proteins have not been identified in apicomplexans, suggesting that SRCAP is recruited differently to the promoter [22]. Furthermore a homologue to yeast histone acetylase, GCN5, has been characterised in T. gondii [23,24] and recently shown to be transported to the parasite nucleus by interaction with importin-alpha [25]. This essential histone acetylase is capable of partially complementing a yeast GCN5-mutant.…”

Section: Genome Chromatin Structure and Remodelling Factorsmentioning

confidence: 99%

The transcription machinery and the molecular toolbox to control gene expression in Toxoplasma gondii and other protozoan parasites

Meissner¹,

Soldati

2005

Microbes and Infection

View full text Add to dashboard Cite

The phylum of Apicomplexa groups a large variety of obligate intracellular protozoan parasites that exhibit complicated life cycles, involving transmission and differentiation within and between different hosts. Little is known about the level of regulation and the nature of the factors controlling gene expression throughout their life stages. Unravelling the mechanisms that govern gene regulation is critical for the development of adequate tools to manipulate these parasites and modulate gene expression, in order to study their function in molecular terms in vivo. A comparative analysis of the transcriptional machinery of several apicomplexan genomes and other protozoan parasites has revealed the existence of a primitive eukaryotic transcription apparatus consisting only of a subset of the general transcription factors found in higher eukaryotes. These findings have some direct implications on development of tools.

show abstract

Cloning and analysis of a Toxoplasma gondii histone acetyltransferase: a novel chromatin remodelling factor in Apicomplexan parasites

Cited by 31 publications

References 66 publications

Histone-Modifying Complexes Regulate Gene Expression Pertinent to the Differentiation of the Protozoan Parasite Toxoplasma gondii

Histone-Modifying Complexes Regulate Gene Expression Pertinent to the Differentiation of the Protozoan Parasite Toxoplasma gondii

Acetylation of Histones and Transcription-Related Factors

The transcription machinery and the molecular toolbox to control gene expression in Toxoplasma gondii and other protozoan parasites

Contact Info

Product

Resources

About