{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T10:10:05Z","timestamp":1764843005962,"version":"build-2065373602"},"reference-count":99,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T00:00:00Z","timestamp":1749513600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Allergy and Infectious Diseases, National Institutes of Health","award":["R01AI128940"],"award-info":[{"award-number":["R01AI128940"]}]},{"name":"Morsani College of Medicine","award":["R01AI128940"],"award-info":[{"award-number":["R01AI128940"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>GCN5-containing SAGA complex is evolutionarily conserved across yeast, plants, and humans and acts as a general transcription coactivator in the genome-wide regulation of genes. In Plasmodium falciparum, PfGCN5 forms a divergent complex, and the mis-localization of this complex by deleting the PfGCN5 bromodomain (\u0394Brd) causes a plethora of growth defects. To directly test the PfGCN5 function, we performed conditional knockdown (KD) of PfGCN5. Whereas PfGCN5 KD phenotypically recapitulated the \u0394Brd growth defects, it caused fewer transcriptional alterations compared to \u0394Brd. To decipher the mechanism by which PfGCN5 regulates gene expression, we applied a new chromatin landscape analysis tool, CUT&amp;Tag-seq, to map the chromatin localization of PfGCN5 and its deposited histone mark H3K9ac. Compared to ChIP-seq, CUT&amp;Tag-seq identified substantially more H3K9ac peaks in the promoters of its target genes, with the peak intensity positively correlated with the levels of gene expression. CUT&amp;Tag-seq analysis was remarkably more sensitive in mapping chromatin positions of PfGCN5, which colocalized with H3K9ac. The genes enriched with PfGCN5\/H3K9ac signals at their promoters are involved in broad biological processes. Notably, PfGCN5\u2032s positions overlapped with sequence motifs recognized by multiple apetela2 (AP2)-domain-containing transcription factors (AP2 TFs), suggesting that they recruited PfGCN5 to these promoters. Additionally, PfGCN5 was also colocalized with AP2-LT, further validating that AP2-LT is an integral component of the PfGCN5 complex. Collectively, these findings establish PfGCN5 as a master gene regulator in controlling general and parasite-specific cellular processes in this low-branching parasitic protist.<\/jats:p>","DOI":"10.3390\/cells14120876","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T09:59:14Z","timestamp":1749549554000},"page":"876","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["GCN5 Is a Master Regulator of Gene Expression in the Malaria Parasite Plasmodium falciparum"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6779-1888","authenticated-orcid":false,"given":"Amuza Byaruhanga","family":"Lucky","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Morsani College of Medicine, University of South Florida, 3720 Spectrum Blvd, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmad Rushdi","family":"Shakri","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Morsani College of Medicine, University of South Florida, 3720 Spectrum Blvd, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoying","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Morsani College of Medicine, University of South Florida, 3720 Spectrum Blvd, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Min","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Morsani College of Medicine, University of South Florida, 3720 Spectrum Blvd, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Lian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Morsani College of Medicine, University of South Florida, 3720 Spectrum Blvd, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3313-2782","authenticated-orcid":false,"given":"Swamy Rakesh","family":"Adapa","sequence":"additional","affiliation":[{"name":"Center for Global Health and Infectious Diseases Research, College of Public Health, University of South Florida, 3720 Spectrum Blvd, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8982-4169","authenticated-orcid":false,"given":"Rays H. Y.","family":"Jiang","sequence":"additional","affiliation":[{"name":"Center for Global Health and Infectious Diseases Research, College of Public Health, University of South Florida, 3720 Spectrum Blvd, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8338-1974","authenticated-orcid":false,"given":"Liwang","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Morsani College of Medicine, University of South Florida, 3720 Spectrum Blvd, Tampa, FL 33612, USA"},{"name":"Center for Global Health and Infectious Diseases Research, College of Public Health, University of South Florida, 3720 Spectrum Blvd, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengqi","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Global Health and Infectious Diseases Research, College of Public Health, University of South Florida, 3720 Spectrum Blvd, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Miao","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Morsani College of Medicine, University of South Florida, 3720 Spectrum Blvd, Tampa, FL 33612, USA"},{"name":"Center for Global Health and Infectious Diseases Research, College of Public Health, University of South Florida, 3720 Spectrum Blvd, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/cr.2011.22","article-title":"Regulation of chromatin by histone modifications","volume":"21","author":"Bannister","year":"2011","journal-title":"Cell Res."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Marmorstein, R., and Zhou, M.M. (2014). Writers and readers of histone acetylation: Structure, mechanism, and inhibition. Cold Spring Harb. Perspect. Biol., 6.","DOI":"10.1101\/cshperspect.a018762"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1101\/gad.11.13.1640","article-title":"Yeast Gcn5 functions in two multisubunit complexes to acetylate nucleosomal histones: Characterization of an Ada complex and the SAGA (Spt\/Ada) complex","volume":"11","author":"Grant","year":"1997","journal-title":"Genes Dev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s13072-021-00402-x","article-title":"Conservation and diversity of the eukaryotic SAGA coactivator complex across kingdoms","volume":"14","author":"Chen","year":"2021","journal-title":"Epigenetics Chromatin"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/S1097-2765(04)00087-5","article-title":"A genome-wide housekeeping role for TFIID and a highly regulated stress-related role for SAGA in Saccharomyces cerevisiae","volume":"13","author":"Huisinga","year":"2004","journal-title":"Mol. Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1105\/tpc.007922","article-title":"Disruption mutations of ADA2b and GCN5 transcriptional adaptor genes dramatically affect Arabidopsis growth, development, and gene expression","volume":"15","author":"Vlachonasios","year":"2003","journal-title":"Plant Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1101\/gad.250225.114","article-title":"The SAGA coactivator complex acts on the whole transcribed genome and is required for RNA polymerase II transcription","volume":"28","author":"Bonnet","year":"2014","journal-title":"Genes Dev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.molcel.2017.08.016","article-title":"SAGA Is a General Cofactor for RNA Polymerase II Transcription","volume":"68","author":"Baptista","year":"2017","journal-title":"Mol. Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.ceb.2010.03.005","article-title":"Multiple faces of the SAGA complex","volume":"22","author":"Koutelou","year":"2010","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.bbaexp.2006.02.006","article-title":"Physical and functional interactions of Arabidopsis ADA2 transcriptional coactivator proteins with the acetyltransferase GCN5 and with the cold-induced transcription factor CBF1","volume":"1759","author":"Mao","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Moraga, F., and Aquea, F. (2015). Composition of the SAGA complex in plants and its role in controlling gene expression in response to abiotic stresses. Front. Plant Sci., 6.","DOI":"10.3389\/fpls.2015.00865"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.molcel.2021.12.015","article-title":"Glucose starvation induces a switch in the histone acetylome for activation of gluconeogenic and fat metabolism genes","volume":"82","author":"Hsieh","year":"2022","journal-title":"Mol. Cell"},{"key":"ref_13","unstructured":"WHO (2024). Would Malaria Report 2024, WHO."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1126\/science.1103717","article-title":"A comprehensive survey of the Plasmodium life cycle by genomic, transcriptomic, and proteomic analyses","volume":"307","author":"Hall","year":"2005","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Bozdech, Z., Llinas, M., Pulliam, B.L., Wong, E.D., Zhu, J., and DeRisi, J.L. (2003). The transcriptome of the intraerythrocytic developmental cycle of Plasmodium falciparum. PLoS Biol., 1.","DOI":"10.1371\/journal.pbio.0000005"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1126\/science.1087025","article-title":"Discovery of gene function by expression profiling of the malaria parasite life cycle","volume":"301","author":"Zhou","year":"2003","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1101\/gr.2218604","article-title":"Comparative genomics of transcriptional control in the human malaria parasite Plasmodium falciparum","volume":"14","author":"Coulson","year":"2004","journal-title":"Genome Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3994","DOI":"10.1093\/nar\/gki709","article-title":"Discovery of the principal specific transcription factors of Apicomplexa and their implication for the evolution of the AP2-integrase DNA binding domains","volume":"33","author":"Balaji","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Campbell, T.L., De Silva, E.K., Olszewski, K.L., Elemento, O., and Llinas, M. (2010). Identification and genome-wide prediction of DNA binding specificities for the ApiAP2 family of regulators from the malaria parasite. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1001165"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/s41564-021-01045-0","article-title":"The transcriptional regulator HDP1 controls expansion of the inner membrane complex during early sexual differentiation of malaria parasites","volume":"7","author":"Morillo","year":"2022","journal-title":"Nat. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1146\/annurev-micro-032521-041554","article-title":"Epigenetic Regulation and Chromatin Remodeling in Malaria Parasites","volume":"77","author":"Hollin","year":"2023","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"D169","DOI":"10.1093\/nar\/gkr993","article-title":"YeTFaSCo: A database of evaluated yeast transcription factor sequence specificities","volume":"40","author":"Hughes","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1128\/EC.00036-10","article-title":"Chromatin-mediated epigenetic regulation in the malaria parasite Plasmodium falciparum","volume":"9","author":"Cui","year":"2010","journal-title":"Eukaryot. Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.mib.2014.05.007","article-title":"Epigenetic memory takes center stage in the survival strategy of malaria parasites","volume":"20","author":"Voss","year":"2014","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.chom.2008.12.012","article-title":"Genome-wide analysis of heterochromatin associates clonally variant gene regulation with perinuclear repressive centers in malaria parasites","volume":"5","author":"Scherf","year":"2009","journal-title":"Cell Host Microbe"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"9655","DOI":"10.1073\/pnas.0902515106","article-title":"Dynamic histone H3 epigenome marking during the intraerythrocytic cycle of Plasmodium falciparum","volume":"106","author":"Alako","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1101\/gr.169417.113","article-title":"Three-dimensional modeling of the P. falciparum genome during the erythrocytic cycle reveals a strong connection between genome architecture and gene expression","volume":"24","author":"Ay","year":"2014","journal-title":"Genome Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1038\/35039531","article-title":"Frequent ectopic recombination of virulence factor genes in telomeric chromosome clusters of P. falciparum","volume":"407","author":"Bottius","year":"2000","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3183","DOI":"10.1073\/pnas.1810815116","article-title":"Comparative 3D genome organization in apicomplexan parasites","volume":"116","author":"Bunnik","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1038\/s41467-018-04295-5","article-title":"Changes in genome organization of parasite-specific gene families during the Plasmodium transmission stages","volume":"9","author":"Bunnik","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1111\/j.1365-2958.2011.07574.x","article-title":"Heterochromatin formation in bistable chromatin domains controls the epigenetic repression of clonally variant Plasmodium falciparum genes linked to erythrocyte invasion","volume":"80","author":"Crowley","year":"2011","journal-title":"Mol. Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.cell.2005.01.037","article-title":"Telomeric heterochromatin propagation and histone acetylation control mutually exclusive expression of antigenic variation genes in malaria parasites","volume":"121","author":"Ralph","year":"2005","journal-title":"Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1073\/pnas.0609084103","article-title":"Epigenetic memory at malaria virulence genes","volume":"104","author":"Chookajorn","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2596","DOI":"10.1093\/nar\/gkp115","article-title":"Plasmodium falciparum heterochromatin protein 1 binds to tri-methylated histone 3 lysine 9 and is linked to mutually exclusive expression of var genes","volume":"37","author":"Delgadillo","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Flueck, C., Bartfai, R., Volz, J., Niederwieser, I., Salcedo-Amaya, A.M., Alako, B.T., Ehlgen, F., Ralph, S.A., Cowman, A.F., and Bozdech, Z. (2009). Plasmodium falciparum heterochromatin protein 1 marks genomic loci linked to phenotypic variation of exported virulence factors. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000569"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.chom.2014.07.004","article-title":"Heterochromatin protein 1 secures survival and transmission of malaria parasites","volume":"16","author":"Brancucci","year":"2014","journal-title":"Cell Host Microbe"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Gupta, A.P., Chin, W.H., Zhu, L., Mok, S., Luah, Y.H., Lim, E.H., and Bozdech, Z. (2013). Dynamic epigenetic regulation of gene expression during the life cycle of malaria parasite Plasmodium falciparum. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003170"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Bartfai, R., Hoeijmakers, W.A., Salcedo-Amaya, A.M., Smits, A.H., Janssen-Megens, E., Kaan, A., Treeck, M., Gilberger, T.W., Francoijs, K.J., and Stunnenberg, H.G. (2010). H2A.Z demarcates intergenic regions of the Plasmodium falciparum epigenome that are dynamically marked by H3K9ac and H3K4me3. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1001223"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s13072-020-00365-5","article-title":"Histone modifications associated with gene expression and genome accessibility are dynamically enriched at Plasmodium falciparum regulatory sequences","volume":"13","author":"Tang","year":"2020","journal-title":"Epigenetics Chromatin"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1128\/EC.3.2.264-276.2004","article-title":"Plasmodium falciparum histone acetyltransferase, a yeast GCN5 homologue involved in chromatin remodeling","volume":"3","author":"Fan","year":"2004","journal-title":"Eukaryot. Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1128\/EC.00062-07","article-title":"PfGCN5-mediated histone H3 acetylation plays a key role in gene expression in Plasmodium falciparum","volume":"6","author":"Cui","year":"2007","journal-title":"Eukaryot. Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1111\/j.1365-2958.2010.07371.x","article-title":"The MYST family histone acetyltransferase regulates gene expression and cell cycle in malaria parasite Plasmodium falciparum","volume":"78","author":"Miao","year":"2010","journal-title":"Mol. Microbiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1016\/j.ijpara.2008.01.002","article-title":"Histone lysine methyltransferases and demethylases in Plasmodium falciparum","volume":"38","author":"Cui","year":"2008","journal-title":"Int. J. Parasitol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1128\/EC.00093-10","article-title":"Epigenetics in Plasmodium: What do we really know?","volume":"9","author":"Merrick","year":"2010","journal-title":"Eukaryot. Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1111\/j.1462-5822.2012.01777.x","article-title":"The role of chromatin in Plasmodium gene expression","volume":"14","author":"Duffy","year":"2012","journal-title":"Cell Microbiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.ijpara.2016.10.008","article-title":"Epigenetic landscapes underlining global patterns of gene expression in the human malaria parasite, Plasmodium falciparum","volume":"47","author":"Gupta","year":"2017","journal-title":"Int. J. Parasitol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1002\/bies.201400145","article-title":"Multiple dimensions of epigenetic gene regulation in the malaria parasite Plasmodium falciparum: Gene regulation via histone modifications, nucleosome positioning and nuclear architecture in P. falciparum","volume":"37","author":"Ay","year":"2015","journal-title":"Bioessays"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.pt.2016.12.004","article-title":"The Role of Chromatin Structure in Gene Regulation of the Human Malaria Parasite","volume":"33","author":"Batugedara","year":"2017","journal-title":"Trends Parasitol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Hollin, T., and Le Roch, K.G. (2020). From Genes to Transcripts, a Tightly Regulated Journey in Plasmodium. Front. Cell. Infect. Microbiol., 10.","DOI":"10.3389\/fcimb.2020.618454"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"11574","DOI":"10.1093\/nar\/gkz1044","article-title":"Epigenetic reader complexes of the human malaria parasite, Plasmodium falciparum","volume":"47","author":"Hoeijmakers","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Miao, J., Wang, C.Q., Lucky, A.B., Liang, X.Y., Min, H., Adapa, S.R., Jiang, R., Kim, K., and Cui, L.W. (2021). A unique GCN5 histone acetyltransferase complex controls erythrocyte invasion and virulence in the malaria parasite Plasmodium falciparum. PLoS Pathog., 17.","DOI":"10.1101\/2021.02.03.429532"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"9411","DOI":"10.1074\/jbc.M809617200","article-title":"The Gcn5 bromodomain of the SAGA complex facilitates cooperative and cross-tail acetylation of nucleosomes","volume":"284","author":"Li","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1128\/EC.00063-08","article-title":"Histone acetyltransferase inhibitor anacardic acid causes changes in global gene expression during in vitro Plasmodium falciparum development","volume":"7","author":"Cui","year":"2008","journal-title":"Eukaryot. Cell"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e00577-23","DOI":"10.1128\/aac.00577-23","article-title":"Plasmodium falciparum GCN5 plays a key role in regulating artemisinin resistance-related stress responses","volume":"67","author":"Lucky","year":"2023","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"jcs236489","DOI":"10.1242\/jcs.236489","article-title":"Plasmodium falciparum GCN5 acetyltransferase follows a novel proteolytic processing pathway that is essential for its function","volume":"133","author":"Bhowmick","year":"2020","journal-title":"J. Cell Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1038\/s41467-019-09982-5","article-title":"CUT&Tag for efficient epigenomic profiling of small samples and single cells","volume":"10","author":"Wu","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3264","DOI":"10.1038\/s41596-020-0373-x","article-title":"Efficient low-cost chromatin profiling with CUT&Tag","volume":"15","author":"Janssens","year":"2020","journal-title":"Nat. Protoc."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Lucky, A.B., Wang, C.Q., Liu, M., Liang, X.Y., Min, H., Fan, Q., Siddiqui, F.A., Adapa, S.R., Li, X.L., and Jiang, R.H.Y. (2023). A type II protein arginine methyltransferase regulates merozoite invasion in Plasmodium falciparum. Commun. Biol., 6.","DOI":"10.1038\/s42003-023-05038-z"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/ng1180","article-title":"PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes","volume":"34","author":"Mootha","year":"2003","journal-title":"Nat. Genet."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1083\/jcb.201206112","article-title":"The cellular and molecular basis for malaria parasite invasion of the human red blood cell","volume":"198","author":"Cowman","year":"2012","journal-title":"J. Cell Biol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Flueck, C., Bartfai, R., Niederwieser, I., Witmer, K., Alako, B.T., Moes, S., Bozdech, Z., Jenoe, P., Stunnenberg, H.G., and Voss, T.S. (2010). A major role for the Plasmodium falciparum ApiAP2 protein PfSIP2 in chromosome end biology. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000784"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Sierra-Miranda, M., Vembar, S.S., Delgadillo, D.M., Avila-Lopez, P.A., Herrera-Solorio, A.M., Lozano Amado, D., Vargas, M., and Hernandez-Rivas, R. (2017). PfAP2Tel, harbouring a non-canonical DNA-binding AP2 domain, binds to Plasmodium falciparum telomeres. Cell. Microbiol., 19.","DOI":"10.1111\/cmi.12742"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"102444","DOI":"10.1016\/j.isci.2021.102444","article-title":"The ApiAP2 factor PfAP2-HC is an integral component of heterochromatin in the malaria parasite Plasmodium falciparum","volume":"24","author":"Carrington","year":"2021","journal-title":"iScience"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3413","DOI":"10.1093\/nar\/gkac176","article-title":"Genome-wide landscape of ApiAP2 transcription factors reveals a heterochromatin-associated regulatory network during Plasmodium falciparum blood-stage development","volume":"50","author":"Shang","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2154","DOI":"10.1038\/s41564-023-01497-6","article-title":"DNA-binding protein PfAP2-P regulates parasite pathogenesis during malaria parasite blood stages","volume":"8","author":"Subudhi","year":"2023","journal-title":"Nat. Microbiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/j.chom.2017.05.006","article-title":"Red Blood Cell Invasion by the Malaria Parasite Is Coordinated by the PfAP2-I Transcription Factor","volume":"21","author":"Santos","year":"2017","journal-title":"Cell Host Microbe"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1038\/s41467-020-15026-0","article-title":"Dissecting the role of PfAP2-G in malaria gametocytogenesis","volume":"11","author":"Josling","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nature12920","article-title":"A transcriptional switch underlies commitment to sexual development in malaria parasites","volume":"507","author":"Kafsack","year":"2014","journal-title":"Nature"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.chom.2018.03.007","article-title":"Chromatin Accessibility-Based Characterization of the Gene Regulatory Network Underlying Plasmodium falciparum Blood-Stage Development","volume":"23","author":"Toenhake","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s13072-015-0029-1","article-title":"A comprehensive epigenome map of Plasmodium falciparum reveals unique mechanisms of transcriptional regulation and identifies H3K36me2 as a global mark of gene suppression","volume":"8","author":"Karmodiya","year":"2015","journal-title":"Epigenetics Chromatin"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1093\/bioinformatics\/btr261","article-title":"DREME: Motif discovery in transcription factor ChIP-seq data","volume":"27","author":"Bailey","year":"2011","journal-title":"Bioinformatics"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"10161","DOI":"10.1093\/nar\/gkae585","article-title":"DNA sequence and chromatin differentiate sequence-specific transcription factor binding in the human malaria parasite Plasmodium falciparum","volume":"52","author":"Bonnell","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e00457-20","DOI":"10.1128\/msphere.00457-20","article-title":"Redesigned TetR-Aptamer System to Control Gene Expression in Plasmodium falciparum","volume":"5","author":"Rajaram","year":"2020","journal-title":"mSphere"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"10727","DOI":"10.1038\/ncomms10727","article-title":"Synthetic RNA-protein modules integrated with native translation mechanisms to control gene expression in malaria parasites","volume":"7","author":"Ganesan","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e71636","DOI":"10.7554\/eLife.71636","article-title":"Divergent acyl carrier protein decouples mitochondrial Fe-S cluster biogenesis from fatty acid synthesis in malaria parasites","volume":"10","author":"Falekun","year":"2021","journal-title":"eLife"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Nasamu, A.S., Falla, A., Pasaje, C.F.A., Wall, B.A., Wagner, J.C., Ganesan, S.M., Goldfless, S.J., and Niles, J.C. (2021). An integrated platform for genome engineering and gene expression perturbation in. Sci. Rep., 11.","DOI":"10.1038\/s41598-020-77644-4"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e2204167119","DOI":"10.1073\/pnas.2204167119","article-title":"Identification of basal complex protein that is essential for maturation of transmission-stage malaria parasites","volume":"119","author":"Clements","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"8128","DOI":"10.1074\/jbc.RA118.002552","article-title":"The mitochondrial ribosomal protein L13 is critical for the structural and functional integrity of the mitochondrion in","volume":"293","author":"Ke","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Kudyba, H.M., Cobb, D.W., Vega-Rodr\u00edguez, J., and Muralidharan, V. (2021). Some conditions apply: Systems for studying protein function. PLoS Pathog., 17.","DOI":"10.1371\/journal.ppat.1009442"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Chen, H., Zhang, L., Wang, Q., He, C., Dender, L.F., and Gong, F. (2021). A role for Gcn5 in heterochromatin structure, gene silencing and NER at the HML locus in budding yeast. bioRxiv, bioRxiv:2021.02.28.433071.","DOI":"10.1101\/2021.02.28.433071"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.cell.2005.01.036","article-title":"Heterochromatin silencing and locus repositioning linked to regulation of virulence genes in Plasmodium falciparum","volume":"121","author":"Duraisingh","year":"2005","journal-title":"Cell"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Wang, J., Dixon, S.E., Ting, L.M., Liu, T.K., Jeffers, V., Croken, M.M., Calloway, M., Cannella, D., Hakimi, M.A., and Kim, K. (2014). Lysine acetyltransferase GCN5b interacts with AP2 factors and is required for Toxoplasma gondii proliferation. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1003830"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1038\/s41586-022-05303-x","article-title":"Structure of the NuA4 acetyltransferase complex bound to the nucleosome","volume":"610","author":"Qu","year":"2022","journal-title":"Nature"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2244","DOI":"10.1128\/MCB.01653-07","article-title":"Functional dissection of the NuA4 histone acetyltransferase reveals its role as a genetic hub and that Eaf1 is essential for complex integrity","volume":"28","author":"Mitchell","year":"2008","journal-title":"Mol. Cell. Biol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e00140-24","DOI":"10.1128\/msphere.00140-24","article-title":"MYST regulates DNA repair and forms a NuA4-like complex in the malaria parasite Plasmodium falciparum","volume":"9","author":"Kalamuddin","year":"2024","journal-title":"mSphere"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/nature04104","article-title":"A protein interaction network of the malaria parasite Plasmodium falciparum","volume":"438","author":"LaCount","year":"2005","journal-title":"Nature"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1126\/science.781840","article-title":"Human malaria parasites in continuous culture","volume":"193","author":"Trager","year":"1976","journal-title":"Science"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1038\/nprot.2010.185","article-title":"Rapid isolation of single malaria parasite-infected red blood cells by cell sorting","volume":"6","author":"Miao","year":"2011","journal-title":"Nat. Protoc."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"14378","DOI":"10.1073\/pnas.1009198107","article-title":"Isolation of viable Plasmodium falciparum merozoites to define erythrocyte invasion events and advance vaccine and drug development","volume":"107","author":"Boyle","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1242\/jcs.059824","article-title":"The Puf-family RNA-binding protein PfPuf2 regulates sexual development and sex differentiation in the malaria parasite Plasmodium falciparum","volume":"123","author":"Miao","year":"2010","journal-title":"J. Cell Sci."},{"key":"ref_92","first-page":"3144","article-title":"The RNA-binding protein Puf1 functions in the maintenance of gametocytes in Plasmodium falciparum","volume":"129","author":"Shrestha","year":"2016","journal-title":"J. Cell Sci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.gene.2005.10.022","article-title":"The malaria parasite Plasmodium falciparum histones: Organization, expression, and acetylation","volume":"369","author":"Miao","year":"2006","journal-title":"Gene"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.3317","article-title":"HISAT: A fast spliced aligner with low memory requirements","volume":"12","author":"Kim","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Anders, S., and Huber, W. (2010). Differential expression analysis for sequence count data. Genome Biol., 11.","DOI":"10.1186\/gb-2010-11-10-r106"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"featureCounts: An efficient general purpose program for assigning sequence reads to genomic features","volume":"30","author":"Liao","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.chom.2018.01.008","article-title":"Comparative Heterochromatin Profiling Reveals Conserved and Unique Epigenome Signatures Linked to Adaptation and Development of Malaria Parasites","volume":"23","author":"Fraschka","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"i884","DOI":"10.1093\/bioinformatics\/bty560","article-title":"fastp: An ultra-fast all-in-one FASTQ preprocessor","volume":"34","author":"Chen","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Liu, T., Meyer, C.A., Eeckhoute, J., Johnson, D.S., Bernstein, B.E., Nusbaum, C., Myers, R.M., Brown, M., and Li, W. (2008). Model-based analysis of ChIP-Seq (MACS). Genome Biol., 9.","DOI":"10.1186\/gb-2008-9-9-r137"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/12\/876\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:49:34Z","timestamp":1760032174000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/12\/876"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,10]]},"references-count":99,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["cells14120876"],"URL":"https:\/\/doi.org\/10.3390\/cells14120876","relation":{},"ISSN":["2073-4409"],"issn-type":[{"type":"electronic","value":"2073-4409"}],"subject":[],"published":{"date-parts":[[2025,6,10]]}}}