TgBDP4 is involved in the regulation of a subset of toxoplasma gondii secretory proteins.

Abstract

Bromodomains (BRDs) are protein interaction modules that exclusively recognize acetylation motifs, and are evolutionarily conserved and present in diverse nuclear proteins. Toxoplasma gondii is the causative agent of toxoplasmosis, with the tachyzoite stage driving pathogenesis through rapid invasion and replication within nucleated cells. Bromodomain-containing protein 4 (BDP4) is a conserved BRD protein across apicomplexans. To address the roles of T. gondii bromodomain-containing protein 4 (TgBDP4) in the lytic circle of T. gondii, the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 and an auxin-inducible degron-based conditional knockdown strategy were used to construct a conditional knockdown parasite line. Phenotypic analysis revealed a growth defect in parasite replication when TgBDP4 was depleted conditionally. TgBDP4 localized in the parasite's nucleus. Depletion of the TgBDP4 led to changes in the expression level of 874 genes. The loss of TgBDP4 resulted in widespread dysregulation of gene expression, highlighting its involvement in both transcriptional activation and repression. Notably, perturbation in the expression of seven APiAP2 transcription factors was accompanied by the down-regulation of specific secretory proteins, such as ROP37, ROP15, ROP30, MIC3, and MIC12. These findings suggest that TgBDP4 may be implicated in the regulatory network controlling secretory protein expression.