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However, the regulatory mechanisms governing these life cycle transitions are not well understood. In this study, we investigated the AP2 factor AP2X-1, which is expressed during the tachyzoite and bradyzoite stages but decreases in the mature merozoite stage. Knockout of\n                      <jats:italic toggle=\"yes\">ap2X-1<\/jats:italic>\n                      significantly impaired tachyzoite invasion and replication while increasing the frequency of bradyzoite differentiation. As a component associated with the HDAC3\/MORC complex, loss of\n                      <jats:italic toggle=\"yes\">ap2X-1<\/jats:italic>\n                      led to the upregulation of bradyzoite- and sexual stage-specific genes. Single-cell sequencing revealed that the\n                      <jats:italic toggle=\"yes\">ap2X-1<\/jats:italic>\n                      knockout strain exhibited a mixed population of tachyzoite-, bradyzoite-, merozoite-, and sporozoite-like parasites. Cleavage under targets and tagmentation analysis revealed a substantial overlap between AP2X-1 and the HDAC3\/MORC complex at the promoters of bradyzoite- and sexual stage-specific genes. Additionally, assay for transposase-accessible chromatin with high-throughput sequencing analysis demonstrated that AP2X-1 influences chromatin compaction and accessibility, suggesting that AP2X-1 may modulate the function of the HDAC3\/MORC complex to facilitate the repression of bradyzoite differentiation and sexual commitment. Loss of\n                      <jats:italic toggle=\"yes\">ap2X-1<\/jats:italic>\n                      resulted in significant attenuation of\n                      <jats:italic toggle=\"yes\">T. gondii<\/jats:italic>\n                      virulence and decreased brain cyst formation\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      . These findings identify AP2X-1 as a critical negative regulator of\n                      <jats:italic toggle=\"yes\">T. gondii<\/jats:italic>\n                      sexual development.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        <jats:italic toggle=\"yes\">Toxoplasma gondii<\/jats:italic>\n                        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\n                        <jats:italic toggle=\"yes\">T. gondii<\/jats:italic>\n                        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\n                        <jats:italic toggle=\"yes\">ap2X-1<\/jats:italic>\n                        significantly reduced\n                        <jats:italic toggle=\"yes\">T. gondii<\/jats:italic>\n                        virulence and its ability to form brain cysts. These findings reveal a previously unknown regulatory pathway controlling sexual development in\n                        <jats:italic toggle=\"yes\">T. gondii<\/jats:italic>\n                        , providing new insights into its underlying mechanisms.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.00052-25","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T12:00:27Z","timestamp":1755518427000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["AP2X-1 is a negative regulator of\n                    <i>Toxoplasma gondii<\/i>\n                    sexual commitment"],"prefix":"10.1128","volume":"16","author":[{"given":"Li-Xiu","family":"Sun","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00dg3j745","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory for 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