Transcriptomics

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6

Toxoplasma gondii lysine acetyltransferase GCN5-A functions in the cellular response to alkaline stress and expression of cyst genes


ABSTRACT: Parasitic protozoa such as the apicomplexan Toxoplasma gondii progress through their life cycle in response to stimuli in the environment or host organism. Very little is known about how proliferating tachyzoites reprogram their expressed genome in response to stresses that prompt development into latent bradyzoite cysts. We have previously linked histone acetylation with the expression of stage-specific genes, but the factors involved remain to be determined. We sought to determine if GCN5, which operates as a transcriptional co-activator by virtue of its histone acetyltransferase (HAT) activity, contributed to stress-induced changes in gene expression in Toxoplasma. In contrast to other lower eukaryotes, Toxoplasma has duplicated its GCN5 lysine acetyltransferase (KAT). Disruption of the gene encoding for TgGCN5-A did not produce a severe phenotype under normal culture conditions, but here we show that the TgGCN5-A null mutant is deficient in recovering from alkaline pH, a common stress used to induce bradyzoite differentiation in vitro. The TgGCN5-A knockout is incapable of up-regulating key marker genes expressed during development of the latent cyst form. Complementation of the TgGCN5-A knockout restores the expression of these stress-induced genes and reverses the stress recovery defect. We also describe a genome-wide analysis of the Toxoplasma transcriptional response to alkaline pH stress, finding that TgGCN5-A knockout parasites fail to up-regulate 68% of the stress response genes that are induced 2-fold or more in wild-type. Using chromatin immunoprecipitation, we verify an enrichment of TgGCN5-A at the upstream regions of genes activated by alkaline pH exposure, including developmentally regulated genes. Wild-type and GCN5-A- Knockout organisms were subjected to control and stress treatments

ORGANISM(S): Toxoplasma gondii  

SUBMITTER: Jeanette N McClintick   Arunasalam Naguleswaran  Eliana V Elias  Howard J Edenberg  William J Sullivan 

PROVIDER: E-GEOD-22100 | ArrayExpress | 2011-05-25

SECONDARY ACCESSION(S): GSE22100PRJNA128921

REPOSITORIES: GEO, ArrayExpress

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Publications

Toxoplasma gondii lysine acetyltransferase GCN5-A functions in the cellular response to alkaline stress and expression of cyst genes.

Naguleswaran Arunasalam A   Elias Eliana V EV   McClintick Jeanette J   Edenberg Howard J HJ   Sullivan William J WJ  

PLoS pathogens 20101216 12


Parasitic protozoa such as the apicomplexan Toxoplasma gondii progress through their life cycle in response to stimuli in the environment or host organism. Very little is known about how proliferating tachyzoites reprogram their expressed genome in response to stresses that prompt development into latent bradyzoite cysts. We have previously linked histone acetylation with the expression of stage-specific genes, but the factors involved remain to be determined. We sought to determine if GCN5, whi  ...[more]

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