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AP2X-1 is a negative regulator of Toxoplasma gondii sexual commitment

by Elsheikha, Hany M. , Sun, Li-Xiu , Zheng, Xiao-Nan , Wang, Jin-Lei , Zhang, Tian-Yu , Zhang, Zhi-Wei , Zhu, Xing-Quan , Liu, Guo-Hua , Wang, Meng , Fu, Bao-Quan

in Animals / Antibodies / AP2X-1 / Cell cycle / Chromatin / Compaction / CRISPR / Cysts / Developmental stages / Down-regulation / Experiments / gene expression / Gene Expression Regulation / Gene Knockout Techniques / Genes / HDAC3/MORC complex / Histone Deacetylases - genetics / Histone Deacetylases - metabolism / Life Cycle Stages - genetics / Life cycles / Localization / Mice / Next-generation sequencing / Parasites / Parasitology / Pathogenesis / Promoters / Proteins / Protozoa / Protozoan Proteins - genetics / Protozoan Proteins - metabolism / Research Article / Sequence analysis / sexual development / Statistical analysis / Toxoplasma - genetics / Toxoplasma - growth & development / Toxoplasma - physiology / Toxoplasma gondii / Toxoplasmosis - parasitology / transcription / Transposase / Virulence

2025

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AP2X-1 is a negative regulator of Toxoplasma gondii sexual commitment

by Elsheikha, Hany M. , Sun, Li-Xiu , Zheng, Xiao-Nan , Wang, Jin-Lei , Zhang, Tian-Yu , Zhang, Zhi-Wei , Zhu, Xing-Quan , Liu, Guo-Hua , Wang, Meng , Fu, Bao-Quan

2025

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AP2X-1 is a negative regulator of Toxoplasma gondii sexual commitment

by Elsheikha, Hany M. , Sun, Li-Xiu , Zheng, Xiao-Nan , Wang, Jin-Lei , Zhang, Tian-Yu , Zhang, Zhi-Wei , Zhu, Xing-Quan , Liu, Guo-Hua , Wang, Meng , Fu, Bao-Quan

2025

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Journal Article

AP2X-1 is a negative regulator of Toxoplasma gondii sexual commitment

Elsheikha, Hany M.,

Sun, Li-Xiu,

Zheng, Xiao-Nan,

Wang, Jin-Lei,

Zhang, Tian-Yu,

Zhang, Zhi-Wei,

Zhu, Xing-Quan,

Liu, Guo-Hua,

Wang, Meng,

Fu, Bao-Quan

2025

Overview

Toxoplasma gondii undergoes a complex life cycle characterized by alternating developmental stages. The genetic reprogramming mechanisms driving these stage transitions remain largely unknown. In this study, we identified the AP2 factor AP2X-1 as a critical regulator important for T. gondii growth and life cycle progression. Our findings suggest that AP2X-1 functions as a repressor by modulating the function or influencing the association of the HDAC3/MORC complex at the promoters of bradyzoite- and sexual stage-specific genes, leading to chromatin compaction, restricting DNA accessibility and thereby repressing the transcription of genes required for bradyzoite formation and sexual commitment. Deletion of ap2X-1 significantly reduced T. gondii virulence and its ability to form brain cysts. These findings reveal a previously unknown regulatory pathway controlling sexual development in T. gondii , providing new insights into its underlying mechanisms.

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Publisher

American Society for Microbiology

Subject

/ AP2X-1

/ CRISPR