{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:48:01Z","timestamp":1792100881423,"version":"4.4.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012810","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T00:00:00Z","timestamp":1736467200000}}],"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T00:00:00Z","timestamp":1735516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004794","name":"Centre National de la Recherche Scientifique","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001677","name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100015872","name":"Universit\u00e9 de Lille","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015872","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CPER CTRL Long\u00e9vit\u00e9"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Pathogenesis of <jats:italic>Toxoplasma gondii<\/jats:italic> in the intermediate host is based on the tachyzoite ability to divide rapidly to produce significant amount of daughter cells in a reduce time frame. The regulation of the cell-cycle specific expression program is therefore key to their proliferation. Transcriptional regulation has a crucial role in establishing this expression program and transcription factors regulates many aspects of tachyzoite cell cycle. We explored the role of two ApiAP2 transcription factors, TgAP2XII-9 and TgAP2III-2, during the cell cycle of the tachyzoite form. While TgAP2III-2 has only a minor impact on the tachyzoite proliferation, we show that TgAP2XII-9 regulates many aspects of the cell cycle including the proper assembly of the daughter cells inner membrane complex and temporal expression of many virulence genes. Creation of a double mutant strain for TgAP2XII-9 and TgAP2III-2 shows that TgAP2XII-9 had a prominent role during daughter cell assembly. Using transcriptomics and Cut&amp;Tag, we demonstrate that TgAP2XII-9 mainly acts through the transcriptional control of at least 300 genes promoters. Interestingly, TgAP2XII-9 plays a crucial role repressing the expression of genes necessary for budding initiation and activating genes necessary for microneme <jats:italic>de novo<\/jats:italic> formation. We also explored the importance of the AP2 domain of TgAP2XII-9 demonstrating its critical role to exert its function. Therefore, we showed that TgAP2XII-9 is a crucial transcription factor which is key to daughter cell assembly post budding initiation.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012810","type":"journal-article","created":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T18:52:22Z","timestamp":1735584742000},"page":"e1012810","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Cascading expression of ApiAP2 transcription factors controls daughter cell assembly in Toxoplasma gondii"],"prefix":"10.1371","volume":"20","author":[{"given":"Maanasa","family":"Bhaskaran","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkat","family":"Mudiyam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Mouveaux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Roger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0047-8189","authenticated-orcid":true,"given":"Mathieu","family":"Gissot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,12,30]]},"reference":[{"key":"ppat.1012810.ref001","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1016\/j.micinf.2008.07.015","article-title":"Toxoplasma: the next 100 years","volume":"10","author":"K Kim","year":"2008","journal-title":"Microbes Infect"},{"key":"ppat.1012810.ref002","doi-asserted-by":"crossref","first-page":"273","DOI":"10.2147\/DDDT.S60973","article-title":"Drugs in development for toxoplasmosis: advances, challenges, and current status.","volume":"11","author":"PH Alday","year":"2017","journal-title":"Drug Des Devel Ther."},{"key":"ppat.1012810.ref003","doi-asserted-by":"crossref","first-page":"283","DOI":"10.3389\/fcimb.2021.670049","article-title":"The Modular Circuitry of Apicomplexan Cell Division Plasticity.","volume":"11","author":"MJ Gubbels","year":"2021","journal-title":"Front Cell Infect Microbiol"},{"key":"ppat.1012810.ref004","doi-asserted-by":"crossref","first-page":"2094","DOI":"10.1038\/s44318-024-00095-4","article-title":"The Crk4-Cyc4 complex regulates G2\/M transition in Toxoplasma gondii","volume":"43","author":"LM Hawkins","year":"2024","journal-title":"EMBO Journal"},{"key":"ppat.1012810.ref005","first-page":"35","article-title":"The initiation and early development of the tubulin-containing cytoskeleton in the human parasite Toxoplasma gondii","author":"LF Arias Padilla","year":"2024","journal-title":"Mol Biol Cell"},{"key":"ppat.1012810.ref006","article-title":"The initiation and early development of apical-basal polarity in Toxoplasma gondii","author":"LF Arias Padilla","year":"2024","journal-title":"J Cell Sci"},{"key":"ppat.1012810.ref007","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.ppat.1001029","article-title":"Biogenesis of the inner membrane complex is dependent on vesicular transport by the alveolate specific GTPase Rab11B.","volume":"6","author":"C Agop-Nersesian","year":"2010","journal-title":"PLoS Pathog."},{"key":"ppat.1012810.ref008","doi-asserted-by":"crossref","first-page":"e13","DOI":"10.1371\/journal.ppat.0020013","article-title":"Cytoskeletal Components of an Invasion Machine\u2014The Apical Complex of Toxoplasma gondii.","volume":"2","author":"K Hu","year":"2006","journal-title":"PLoS Pathog."},{"key":"ppat.1012810.ref009","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1091\/mbc.01-06-0309","article-title":"Daughter cell assembly in the protozoan parasite Toxoplasma gondii","volume":"13","author":"K Hu","year":"2002","journal-title":"Mol Biol Cell"},{"key":"ppat.1012810.ref010","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S0166-6851(01)00289-4","article-title":"Characterization of the subpellicular network, a filamentous membrane skeletal component in the parasite Toxoplasma gondii","volume":"115","author":"T Mann","year":"2001","journal-title":"Mol Biochem Parasitol"},{"key":"ppat.1012810.ref011","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0166-6851(01)00284-5","article-title":"Defining the cell cycle for the tachyzoite stage of Toxoplasma gondii","volume":"115","author":"JR Radke","year":"2001","journal-title":"Mol Biochem Parasitol"},{"key":"ppat.1012810.ref012","doi-asserted-by":"crossref","first-page":"209","DOI":"10.2307\/3276925","article-title":"The fine structure and reproduction of Toxoplasma gondii","volume":"54","author":"HG Sheffield","year":"1968","journal-title":"J Parasitol"},{"key":"ppat.1012810.ref013","unstructured":"Tilney LG, Tilney MS, Guild GM. 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