Unveiling the Transcriptional Regulation of Development in Toxoplasma gondii: Insights into a Cascade AP2 Regulatory Network

ABSTRACT: Toxoplasma gondii is a medically and veterinary important intracellular parasite that undergoes distinct developmental transitions in its intermediate and definitive hosts. The switch between stages of T. gondii is meticulously regulated by a variety of factors. Previous studies have explored the role of the microrchidia (MORC) protein complex as a transcriptional suppressor of sexual commitment. By utilizing immunoprecipitation and mass spectrometry, constituents of this protein complex have been identified, including MORC, Histone Deacetylase 3 (HDAC3), and several ApiApiAP2 transcription factors. Conditional knockout of MORC or inhibition of HDAC3 results in upregulation of a set of genes associated with schizogony and sexual stages in T. gondii tachyzoites. Here, our focus extends to three primary ApiAP2s: ApiAP2XII-1, ApiAP2XI-2, and ApiAP2V-2, demonstrating their significant impact on the fitness of asexual tachyzoites and their target genes. Notably, the targeted disruption of ApiAP2XII-1 and ApiAP2XI-2 resulted in a more profound alteration in merozoite-specific genes targeted by the MORC/HDAC3 complex compared to ApiAP2V-2. Additionally, considerable overlap was observed in downstream gene profiles between ApiAP2XII-1 and ApiAP2XI-2, with ApiAP2XII-1 specifically binding to a subset of ApiAP2 transcription factors, including ApiAP2XI-2. These findings reveal an intricate cascade of ApiAP2 regulatory networks involved in T. gondii schizogony development, orchestrated by ApiAP2XII-1 and ApiAP2XI-2. This study provides valuable insights into the transcriptional regulation of T. gondii growth and development, shedding light on the intricate life cycle of this parasitic pathogen.

ORGANISM(S): Toxoplasma gondii

PROVIDER: GSE249604 | GEO | 2023/12/10

REPOSITORIES: GEO