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Epigenetic regulation is one of the mechanisms controlling gene expression and plays an essential role in all organisms. Lysine deacetylases (KDACs) act as epigenetic regulators affecting gene silencing in many eukaryotes. Here, we focus on TgKDAC4, an enzyme unique to apicomplexan parasites, and a class IV KDAC, the least-studied class of deacetylases so far. This enzyme shares only a portion of the specific KDAC domain with other organisms. Phylogenetic analysis from the TgKDAC4 domain shows a putative prokaryotic origin. Surprisingly, TgKDAC4 is located in the apicoplast, making it the only KDAC found in this organelle to date. Transmission electron microscopy assays confirmed the presence of TgKDAC4 in the periphery of the apicoplast. We identified possible targets or\/and partners of TgKDAC4 by immunoprecipitation assays followed by mass spectrometry analysis, including TgCPN60 and TgGAPDH2, both located at the apicoplast and containing acetylation sites. Understanding how the protein works could provide new insights into the metabolism of the apicoplast, an essential organelle for parasite survival.<\/jats:p>","DOI":"10.3390\/microorganisms11061558","type":"journal-article","created":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T01:28:21Z","timestamp":1686533301000},"page":"1558","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["TgKDAC4: A Unique Deacetylase of Toxoplasma\u2019s Apicoplast"],"prefix":"10.3390","volume":"11","author":[{"given":"Mariana Sayuri Ishikawa","family":"Fragoso","sequence":"first","affiliation":[{"name":"Instituto Carlos Chagas, Funda\u00e7\u00e3o Oswaldo Cruz, Curitiba 81350-010, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline Moraes","family":"de Siqueira","sequence":"additional","affiliation":[{"name":"Instituto Carlos Chagas, Funda\u00e7\u00e3o Oswaldo Cruz, Curitiba 81350-010, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8543-2299","authenticated-orcid":false,"given":"Francisca Nath\u00e1lia Luna","family":"Vitorino","sequence":"additional","affiliation":[{"name":"Special Laboratory of Cell Cycle, Center of Toxins, Immune Response and Cell Signalling (CeTICS), Instituto Butantan, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4711-9255","authenticated-orcid":false,"given":"Alexandre Zanatta","family":"Vieira","sequence":"additional","affiliation":[{"name":"Instituto Carlos Chagas, Funda\u00e7\u00e3o Oswaldo Cruz, Curitiba 81350-010, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0925-6953","authenticated-orcid":false,"given":"\u00c9rica Santos","family":"Martins-Duarte","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helisson","family":"Faoro","sequence":"additional","affiliation":[{"name":"Instituto Carlos Chagas, Funda\u00e7\u00e3o Oswaldo Cruz, Curitiba 81350-010, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00falia Pinheiro Chagas","family":"da Cunha","sequence":"additional","affiliation":[{"name":"Special Laboratory of Cell Cycle, Center of Toxins, Immune Response and Cell Signalling (CeTICS), Instituto Butantan, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5221-261X","authenticated-orcid":false,"given":"Andr\u00e9a Rodrigues","family":"\u00c1vila","sequence":"additional","affiliation":[{"name":"Instituto Carlos Chagas, Funda\u00e7\u00e3o Oswaldo Cruz, Curitiba 81350-010, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1387-8096","authenticated-orcid":false,"given":"Sheila Cristina","family":"Nardelli","sequence":"additional","affiliation":[{"name":"Instituto Carlos Chagas, Funda\u00e7\u00e3o Oswaldo Cruz, Curitiba 81350-010, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1126\/science.1175371","article-title":"Lysine Acetylation Targets Protein Complexes and Co-Regulates Major Cellular Functions","volume":"325","author":"Choudhary","year":"2009","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1042\/bj0870258","article-title":"The Presence of Acetyl Groups in Histones","volume":"87","author":"Philllips","year":"1963","journal-title":"Biochem. 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