{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T16:26:48Z","timestamp":1781886408553,"version":"3.54.5"},"reference-count":67,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T00:00:00Z","timestamp":1748390400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T00:00:00Z","timestamp":1748390400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Deutsches Krebsforschungszentrum (DKFZ)"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>The life cycle of <jats:italic>Plasmodium<\/jats:italic> parasites involves intricate, multistage processes that are tightly regulated by stage-specific transcription factors. These factors bind to regulatory regions within gene promoters, enabling the precise expression of genes required for each developmental stage. Despite the importance of these transcriptional mechanisms, our understanding remains limited, particularly in the rodent model organism <jats:italic>P. berghei.<\/jats:italic> To address this, we conducted a genome-wide analysis of RNA-Seq data from different developmental stages of <jats:italic>P. berghei<\/jats:italic> by initially integrating data from human malaria parasites <jats:italic>P. falciparum<\/jats:italic> and <jats:italic>P. vivax<\/jats:italic>. We identified unique transcriptional signatures across <jats:italic>Plasmodium<\/jats:italic> species. Our analysis of <jats:italic>P. berghei<\/jats:italic> revealed stage-specific gene sets clustered by expression profiles and predicted regulatory motifs involved in their control. We interpreted these motifs using known binding sites for eukaryotic transcription factors including ApiAP2 proteins. Additionally, we expanded the annotation of the AGGTAA motif which resembles a de novo motif linked to erythrocytic development in <jats:italic>P. falciparum<\/jats:italic>, and identified its potential interacting proteins including members of the PfMORC and GCN5 complexes. This study enhances our understanding of gene regulation in P. berghei and provides new insights into the transcriptional dynamics underlying <jats:italic>Plasmodium<\/jats:italic> development.<\/jats:p>","DOI":"10.1038\/s41598-025-03586-4","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T07:47:23Z","timestamp":1748418443000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Transcriptome analysis reveals a de novo DNA element that may interact with chromatin-associated proteins in Plasmodium berghei during erythrocytic development"],"prefix":"10.1038","volume":"15","author":[{"given":"Adaobi","family":"Okafor","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yagoub","family":"Adam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedikt","family":"Brors","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezekiel","family":"Adebiyi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,28]]},"reference":[{"key":"3586_CR1","unstructured":"Malaria. Malaria. World Health Organization Available. Retrieved from https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/malaria (2023)."},{"key":"3586_CR2","unstructured":"Cummings, R. D., Hokke, C. H., & Haslam, S. M. Parasitic Infections. In Essentials of Glycobiology 4th edn, (Eds. Varki, A., Cummings, RD., Esko, JD., Stanley, P., Hart, GW., Aebi, M., Mohnen, D., Kinoshita, T., Packer, NH., Prestegard, JH., Schnaar, RL. & Seeberger, PH.)\u00a0(Cold Spring Harbor Laboratory Press, 2022). http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK579956\/\u00a0"},{"issue":"1","key":"3586_CR3","doi-asserted-by":"publisher","first-page":"2656","DOI":"10.1038\/s41467-018-04966-3","volume":"9","author":"HJ Painter","year":"2018","unstructured":"Painter, H. J. et al. Genome-wide real-time in vivo transcriptional dynamics during Plasmodium falciparum blood-stage development. Nat. Commun. 9(1), 2656. https:\/\/doi.org\/10.1038\/s41467-018-04966-3 (2018).","journal-title":"Nat. Commun."},{"issue":"13","key":"3586_CR4","doi-asserted-by":"publisher","first-page":"3994","DOI":"10.1093\/nar\/gki709","volume":"33","author":"S Balaji","year":"2005","unstructured":"Balaji, S. Discovery of the principal specific transcription factors of Apicomplexa and their implication for the evolution of the AP2-integrase DNA binding domains. Nucl. Acid. Res. 33(13), 3994\u20134006. https:\/\/doi.org\/10.1093\/nar\/gki709 (2005).","journal-title":"Nucl. Acid. Res."},{"issue":"11","key":"3586_CR5","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1016\/j.pt.2024.09.007","volume":"40","author":"R Singhal","year":"2024","unstructured":"Singhal, R., Prata, I. O., Bonnell, V. A. & Llin\u00e1s, M. Unraveling the complexities of ApiAP2 regulation in Plasmodium falciparum. Trend. Parasitol. 40(11), 987\u2013999. https:\/\/doi.org\/10.1016\/j.pt.2024.09.007 (2024).","journal-title":"Trend. Parasitol."},{"issue":"10","key":"3586_CR6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001165","volume":"6","author":"TL Campbell","year":"2010","unstructured":"Campbell, T. L., De Silva, E. K., Olszewski, K. L., Elemento, O. & Llin\u00e1s, M. Identification and genome-wide prediction of DNA binding specificities for the ApiAP2 family of regulators from the malaria parasite. PLoS Pathog. 6(10), e1001165. https:\/\/doi.org\/10.1371\/journal.ppat.1001165 (2010).","journal-title":"PLoS Pathog."},{"issue":"6","key":"3586_CR7","doi-asserted-by":"publisher","first-page":"3413","DOI":"10.1093\/nar\/gkac176","volume":"50","author":"X Shang","year":"2022","unstructured":"Shang, X. et al. Genome-wide landscape of ApiAP2 transcription factors reveals a heterochromatin-associated regulatory network during Plasmodium falciparum blood-stage development. Nucl. Acid. Res. 50(6), 3413\u20133431. https:\/\/doi.org\/10.1093\/nar\/gkac176 (2022).","journal-title":"Nucl. Acid. Res."},{"issue":"1","key":"3586_CR8","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1111\/j.1365-2958.2009.07026.x","volume":"76","author":"TD Otto","year":"2010","unstructured":"Otto, T. D. et al. New insights into the blood-stage transcriptome of Plasmodium falciparum using RNA-Seq. Mol. Microbiol. 76(1), 12\u201324. https:\/\/doi.org\/10.1111\/j.1365-2958.2009.07026.x (2010).","journal-title":"Mol. Microbiol."},{"issue":"1","key":"3586_CR9","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1186\/s12915-014-0086-0","volume":"12","author":"TD Otto","year":"2014","unstructured":"Otto, T. D. et al. A comprehensive evaluation of rodent malaria parasite genomes and gene expression. BMC Biol. 12(1), 86. https:\/\/doi.org\/10.1186\/s12915-014-0086-0 (2014).","journal-title":"BMC Biol."},{"key":"3586_CR10","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.33105","volume":"7","author":"AJ Reid","year":"2018","unstructured":"Reid, A. J. et al. Single-cell RNA-seq reveals hidden transcriptional variation in malaria parasites. Elife 7, e33105. https:\/\/doi.org\/10.7554\/eLife.33105 (2018).","journal-title":"Elife"},{"key":"3586_CR11","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaw2619","author":"VM Howick","year":"2019","unstructured":"Howick, V. M. et al. The malaria cell atlas: Single parasite transcriptomes across the complete Plasmodium life cycle. Science https:\/\/doi.org\/10.1126\/science.aaw2619 (2019).","journal-title":"Science"},{"issue":"1","key":"3586_CR12","doi-asserted-by":"publisher","first-page":"3196","DOI":"10.1038\/s41467-021-23434-z","volume":"12","author":"E Real","year":"2021","unstructured":"Real, E. et al. A single-cell atlas of Plasmodium falciparum transmission through the mosquito. Nat. Commun. 12(1), 3196. https:\/\/doi.org\/10.1038\/s41467-021-23434-z (2021).","journal-title":"Nat. Commun."},{"key":"3586_CR13","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.604129","volume":"11","author":"K Witmer","year":"2021","unstructured":"Witmer, K. et al. Using scRNA-seq to Identify transcriptional variation in the malaria parasite ookinete stage. Front. Cell. Infect. Microbiol. 11, 604129. https:\/\/doi.org\/10.3389\/fcimb.2021.604129 (2021).","journal-title":"Front. Cell. Infect. Microbiol."},{"issue":"8","key":"3586_CR14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0010633","volume":"16","author":"AA Ruberto","year":"2022","unstructured":"Ruberto, A. A. et al. Single-cell RNA sequencing of Plasmodium vivax sporozoites reveals stage- and species-specific transcriptomic signatures. PLoS Negl. Trop. Dis. 16(8), e0010633. https:\/\/doi.org\/10.1371\/journal.pntd.0010633 (2022).","journal-title":"PLoS Negl. Trop. Dis."},{"issue":"6695","key":"3586_CR15","doi-asserted-by":"publisher","DOI":"10.1126\/science.adj4088","volume":"384","author":"SK Dogga","year":"2024","unstructured":"Dogga, S. K. et al. A single cell atlas of sexual development in Plasmodium falciparum. Science (New York, N.Y.) 384(6695), eadj4088. https:\/\/doi.org\/10.1126\/science.adj4088 (2024).","journal-title":"Science (New York, N.Y.)"},{"issue":"1","key":"3586_CR16","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1186\/s12936-019-2968-7","volume":"18","author":"R Caldelari","year":"2019","unstructured":"Caldelari, R. et al. Transcriptome analysis of Plasmodium berghei during exo-erythrocytic development. Malar. J. 18(1), 330. https:\/\/doi.org\/10.1186\/s12936-019-2968-7 (2019).","journal-title":"Malar. J."},{"issue":"1","key":"3586_CR17","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1038\/nprot.2006.53","volume":"1","author":"CJ Janse","year":"2006","unstructured":"Janse, C. J., Ramesar, J. & Waters, A. P. High-efficiency transfection and drug selection of genetically transformed blood stages of the rodent malaria parasite Plasmodium berghei. Nat. Protoc. 1(1), 346\u2013356. https:\/\/doi.org\/10.1038\/nprot.2006.53 (2006).","journal-title":"Nat. Protoc."},{"issue":"1","key":"3586_CR18","doi-asserted-by":"publisher","first-page":"e03234","DOI":"10.1128\/mBio.03234-19","volume":"11","author":"M Toro-Moreno","year":"2020","unstructured":"Toro-Moreno, M., Sylvester, K., Srivastava, T., Posfai, D. & Derbyshire, E. R. RNA-seq analysis illuminates the early stages of Plasmodium liver infection. MBio 11(1), e03234-e3319. https:\/\/doi.org\/10.1128\/mBio.03234-19 (2020).","journal-title":"MBio"},{"key":"3586_CR19","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/j.ebiom.2016.04.011","volume":"7","author":"R Hoo","year":"2016","unstructured":"Hoo, R. et al. Integrated analysis of the plasmodium species transcriptome. EBioMedicine 7, 255\u2013266. https:\/\/doi.org\/10.1016\/j.ebiom.2016.04.011 (2016).","journal-title":"EBioMedicine"},{"key":"3586_CR20","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1186\/1471-2164-9-70","volume":"9","author":"JA Young","year":"2008","unstructured":"Young, J. A. et al. In silico discovery of transcription regulatory elements in Plasmodium falciparum. BMC Genomics 9, 70. https:\/\/doi.org\/10.1186\/1471-2164-9-70 (2008).","journal-title":"BMC Genomics"},{"issue":"2","key":"3586_CR21","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.molcel.2007.09.027","volume":"28","author":"O Elemento","year":"2007","unstructured":"Elemento, O., Slonim, N. & Tavazoie, S. A universal framework for regulatory element discovery across all genomes and data types. Mol. Cell 28(2), 337\u2013350. https:\/\/doi.org\/10.1016\/j.molcel.2007.09.027 (2007).","journal-title":"Mol. Cell"},{"issue":"Database issue","key":"3586_CR22","doi-asserted-by":"publisher","first-page":"D19","DOI":"10.1093\/nar\/gkq1019","volume":"39","author":"R Leinonen","year":"2011","unstructured":"Leinonen, R., Sugawara, H., Shumway, M., International Nucleotide Sequence Database Collaboration. The sequence read archive. Nucl. Acid. Res. 39(Database issue), D19-21. https:\/\/doi.org\/10.1093\/nar\/gkq1019 (2011).","journal-title":"Nucl. Acid. Res."},{"issue":"D1","key":"3586_CR23","doi-asserted-by":"publisher","first-page":"D689","DOI":"10.1093\/nar\/gkz890","volume":"48","author":"KL Howe","year":"2020","unstructured":"Howe, K. L. et al. Ensembl Genomes 2020-enabling non-vertebrate genomic research. Nucl. Acid. Res. 48(D1), D689\u2013D695. https:\/\/doi.org\/10.1093\/nar\/gkz890 (2020).","journal-title":"Nucl. Acid. Res."},{"key":"3586_CR24","unstructured":"Andrews, S. FastQC A Quality Control tool for High Throughput Sequence Data. https:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc\/ (2010)."},{"issue":"15","key":"3586_CR25","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","volume":"30","author":"AM Bolger","year":"2014","unstructured":"Bolger, A. M., Lohse, M. & Usadel, B. Trimmomatic: A flexible trimmer for Illumina sequence data. Bioinformatics (Oxford, England) 30(15), 2114\u20132120. https:\/\/doi.org\/10.1093\/bioinformatics\/btu170 (2014).","journal-title":"Bioinformatics (Oxford, England)"},{"issue":"1","key":"3586_CR26","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","volume":"29","author":"A Dobin","year":"2013","unstructured":"Dobin, A. et al. STAR: Ultrafast universal RNA-seq aligner. Bioinformatics (Oxford, England) 29(1), 15\u201321. https:\/\/doi.org\/10.1093\/bioinformatics\/bts635 (2013).","journal-title":"Bioinformatics (Oxford, England)"},{"issue":"1","key":"3586_CR27","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/s12859-022-04572-7","volume":"23","author":"B Signal","year":"2022","unstructured":"Signal, B. & Kahlke, T. How_are_we_stranded_here: Quick determination of RNA-Seq strandedness. BMC Bioinformatics 23(1), 49. https:\/\/doi.org\/10.1186\/s12859-022-04572-7 (2022).","journal-title":"BMC Bioinformatics"},{"issue":"7","key":"3586_CR28","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","volume":"30","author":"Y Liao","year":"2014","unstructured":"Liao, Y., Smyth, G. K. & Shi, W. featureCounts: An efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics (Oxford, England) 30(7), 923\u2013930. https:\/\/doi.org\/10.1093\/bioinformatics\/btt656 (2014).","journal-title":"Bioinformatics (Oxford, England)"},{"issue":"12","key":"3586_CR29","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15(12), 550. https:\/\/doi.org\/10.1186\/s13059-014-0550-8 (2014).","journal-title":"Genome Biol."},{"key":"3586_CR30","doi-asserted-by":"publisher","unstructured":"Smyth, G. K. Limma: Linear models for microarray data. In Bioinformatics and Computational Biology Solutions Using R and Bioconductor 397\u2013420 (springer, New York, NY, 2005). https:\/\/doi.org\/10.1007\/0-387-29362-0_23","DOI":"10.1007\/0-387-29362-0_23"},{"issue":"1","key":"3586_CR31","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","volume":"57","author":"Y Benjamini","year":"1995","unstructured":"Benjamini, Y. & Hochberg, Y. Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing. J. R. Stat. Soc. Ser. B Stat Methodol. 57(1), 289\u2013300. https:\/\/doi.org\/10.1111\/j.2517-6161.1995.tb02031.x (1995).","journal-title":"J. R. Stat. Soc. Ser. B Stat Methodol."},{"key":"3586_CR32","unstructured":"Draw Venn Diagram. (n.d.). Draw Venn Diagram. https:\/\/bioinformatics.psb.ugent.be\/webtools\/Venn\/"},{"key":"3586_CR33","doi-asserted-by":"publisher","unstructured":"Wickham, H. Ggplot2 (Springer New York, NY, n.d.). https:\/\/doi.org\/10.1007\/978-0-387-98141-3","DOI":"10.1007\/978-0-387-98141-3"},{"issue":"18","key":"3586_CR34","doi-asserted-by":"publisher","first-page":"2847","DOI":"10.1093\/bioinformatics\/btw313","volume":"32","author":"Z Gu","year":"2016","unstructured":"Gu, Z., Eils, R. & Schlesner, M. Complex heatmaps reveal patterns and correlations in multidimensional genomic data. Bioinformatics (Oxford, England) 32(18), 2847\u20132849. https:\/\/doi.org\/10.1093\/bioinformatics\/btw313 (2016).","journal-title":"Bioinformatics (Oxford, England)"},{"issue":"Database issue","key":"3586_CR35","doi-asserted-by":"publisher","first-page":"D539","DOI":"10.1093\/nar\/gkn814","volume":"37","author":"C Aurrecoechea","year":"2009","unstructured":"Aurrecoechea, C. et al. PlasmoDB: A functional genomic database for malaria parasites. Nucl. Acid. Res. 37(Database issue), D539-543. https:\/\/doi.org\/10.1093\/nar\/gkn814 (2009).","journal-title":"Nucl. Acid. Res."},{"issue":"7","key":"3586_CR36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0021800","volume":"6","author":"F Supek","year":"2011","unstructured":"Supek, F., Bo\u0161njak, M., \u0160kunca, N. & \u0160muc, T. REVIGO summarizes and visualizes long lists of gene ontology terms. PLoS ONE 6(7), e21800. https:\/\/doi.org\/10.1371\/journal.pone.0021800 (2011).","journal-title":"PLoS ONE"},{"key":"3586_CR37","unstructured":"Kassambara, A., & Mundt, F. factoextra: Extract and Visualize the Results of Multivariate Data Analyses. https:\/\/CRAN.R-project.org\/package=factoextra (n.d.)."},{"issue":"W1","key":"3586_CR38","doi-asserted-by":"publisher","first-page":"W209","DOI":"10.1093\/nar\/gky317","volume":"46","author":"NTT Nguyen","year":"2018","unstructured":"Nguyen, N. T. T. et al. RSAT 2018: Regulatory sequence analysis tools 20th anniversary. Nucl. Acid. Res. 46(W1), W209\u2013W214. https:\/\/doi.org\/10.1093\/nar\/gky317 (2018).","journal-title":"Nucl. Acid. Res."},{"issue":"W1","key":"3586_CR39","doi-asserted-by":"publisher","first-page":"W39","DOI":"10.1093\/nar\/gkv416","volume":"43","author":"TL Bailey","year":"2015","unstructured":"Bailey, T. L., Johnson, J., Grant, C. E. & Noble, W. S. The meme suite. Nucl. Acid. Res. 43(W1), W39-49. https:\/\/doi.org\/10.1093\/nar\/gkv416 (2015).","journal-title":"Nucl. Acid. Res."},{"issue":"D1","key":"3586_CR40","doi-asserted-by":"publisher","first-page":"D165","DOI":"10.1093\/nar\/gkab1113","volume":"50","author":"JA Castro-Mondragon","year":"2022","unstructured":"Castro-Mondragon, J. A. et al. JASPAR 2022: The 9th release of the open-access database of transcription factor binding profiles. Nucl. Acid. Res. 50(D1), D165\u2013D173. https:\/\/doi.org\/10.1093\/nar\/gkab1113 (2022).","journal-title":"Nucl. Acid. Res."},{"issue":"4","key":"3586_CR41","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1016\/j.chom.2018.03.007","volume":"23","author":"CG Toenhake","year":"2018","unstructured":"Toenhake, C. G. et al. Chromatin accessibility-based characterization of the gene regulatory network underlying Plasmodium falciparum blood-stage development. Cell Host. Microbe. 23(4), 557-569.e9. https:\/\/doi.org\/10.1016\/j.chom.2018.03.007 (2018).","journal-title":"Cell Host. Microbe."},{"issue":"11","key":"3586_CR42","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","volume":"13","author":"P Shannon","year":"2003","unstructured":"Shannon, P. et al. Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome. Res. 13(11), 2498\u20132504. https:\/\/doi.org\/10.1101\/gr.1239303 (2003).","journal-title":"Genome. Res."},{"issue":"5","key":"3586_CR43","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1038\/ng.375","volume":"41","author":"H Suzuki","year":"2009","unstructured":"FANTOM Consortium et al. The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line. Nat. Genet. 41(5), 553\u2013562. https:\/\/doi.org\/10.1038\/ng.375 (2009).","journal-title":"Nat. Genet."},{"issue":"5","key":"3586_CR44","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1101\/gr.169508.113","volume":"24","author":"PJ Balwierz","year":"2014","unstructured":"Balwierz, P. J. et al. ISMARA: Automated modeling of genomic signals as a democracy of regulatory motifs. Genome Res. 24(5), 869\u2013884. https:\/\/doi.org\/10.1101\/gr.169508.113 (2014).","journal-title":"Genome Res."},{"key":"3586_CR45","doi-asserted-by":"publisher","DOI":"10.1101\/2021.08.23.457422","author":"TL Bailey","year":"2021","unstructured":"Bailey, T. L. & Grant, C. E. SEA: Simple enrichment analysis of motifs. Bioinformatics https:\/\/doi.org\/10.1101\/2021.08.23.457422 (2021).","journal-title":"Bioinformatics"},{"issue":"9","key":"3586_CR46","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.1093\/bioinformatics\/btx657","volume":"34","author":"T Galili","year":"2018","unstructured":"Galili, T., O\u2019Callaghan, A., Sidi, J. & Sievert, C. heatmaply: An R package for creating interactive cluster heatmaps for online publishing. Bioinformatics (Oxford, England) 34(9), 1600\u20131602. https:\/\/doi.org\/10.1093\/bioinformatics\/btx657 (2018).","journal-title":"Bioinformatics (Oxford, England)"},{"key":"3586_CR47","doi-asserted-by":"publisher","unstructured":"Hennig, C. fpc: Flexible Procedures for Clustering (p. 2.2\u201313) . https:\/\/doi.org\/10.32614\/CRAN.package.fpc (2003)","DOI":"10.32614\/CRAN.package.fpc"},{"issue":"10","key":"3586_CR48","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.1093\/bioinformatics\/btw024","volume":"32","author":"G Tan","year":"2016","unstructured":"Tan, G. & Lenhard, B. TFBSTools: An R\/bioconductor package for transcription factor binding site analysis. Bioinformatics 32(10), 1555\u20131556. https:\/\/doi.org\/10.1093\/bioinformatics\/btw024 (2016).","journal-title":"Bioinformatics"},{"key":"3586_CR49","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.92499.2","author":"Z Chahine","year":"2024","unstructured":"Chahine, Z. et al. PfMORC protein regulates chromatin accessibility and transcriptional repression in the human malaria parasite. Plasmodium falciparum https:\/\/doi.org\/10.7554\/eLife.92499.2 (2024).","journal-title":"Plasmodium falciparum"},{"issue":"12","key":"3586_CR50","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1186\/s13059-014-0547-3","volume":"15","author":"X Zhou","year":"2014","unstructured":"Zhou, X. et al. Epigenetic modifications are associated with inter-species gene expression variation in primates. Genome Biol. 15(12), 547. https:\/\/doi.org\/10.1186\/s13059-014-0547-3 (2014).","journal-title":"Genome Biol."},{"issue":"1","key":"3586_CR51","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.chom.2016.12.003","volume":"21","author":"K Modrzynska","year":"2017","unstructured":"Modrzynska, K. et al. A knockout screen of ApiAP2 genes reveals networks of interacting transcriptional regulators controlling the Plasmodium life cycle. Cell Host. Microb. 21(1), 11\u201322. https:\/\/doi.org\/10.1016\/j.chom.2016.12.003 (2017).","journal-title":"Cell Host. Microb."},{"issue":"13","key":"3586_CR52","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx314","volume":"45","author":"JA Castro-Mondragon","year":"2017","unstructured":"Castro-Mondragon, J. A., Jaeger, S., Thieffry, D., Thomas-Chollier, M. & van Helden, J. RSAT matrix-clustering: Dynamic exploration and redundancy reduction of transcription factor binding motif collections. Nucl. Acid. Res. 45(13), e119. https:\/\/doi.org\/10.1093\/nar\/gkx314 (2017).","journal-title":"Nucl. Acid. Res."},{"issue":"2","key":"3586_CR53","doi-asserted-by":"publisher","first-page":"47","DOI":"10.3390\/pathogens8020047","volume":"8","author":"MD Jeninga","year":"2019","unstructured":"Jeninga, M. D., Quinn, J. E. & Petter, M. ApiAP2 transcription factors in apicomplexan parasites. Pathogens (Basel, Switzerland) 8(2), 47. https:\/\/doi.org\/10.3390\/pathogens8020047 (2019).","journal-title":"Pathogens (Basel, Switzerland)"},{"issue":"6","key":"3586_CR54","doi-asserted-by":"publisher","first-page":"1635","DOI":"10.1016\/j.celrep.2019.07.019","volume":"28","author":"C Hillier","year":"2019","unstructured":"Hillier, C. et al. Landscape of the Plasmodium interactome reveals both conserved and species-specific functionality. Cell Rep. 28(6), 1635-1647.e5. https:\/\/doi.org\/10.1016\/j.celrep.2019.07.019 (2019).","journal-title":"Cell Rep."},{"key":"3586_CR55","doi-asserted-by":"publisher","first-page":"RP92201","DOI":"10.7554\/eLife.92201","volume":"12","author":"MK Singh","year":"2024","unstructured":"Singh, M. K. et al. A Plasmodium falciparum MORC protein complex modulates epigenetic control of gene expression through interaction with heterochromatin. Elife 12, RP92201. https:\/\/doi.org\/10.7554\/eLife.92201 (2024).","journal-title":"Elife"},{"issue":"7064","key":"3586_CR56","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1038\/nature04104","volume":"438","author":"DJ LaCount","year":"2005","unstructured":"LaCount, D. J. et al. A protein interaction network of the malaria parasite Plasmodium falciparum. Nature 438(7064), 103\u2013107. https:\/\/doi.org\/10.1038\/nature04104 (2005).","journal-title":"Nature"},{"issue":"6","key":"3586_CR57","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1016\/j.chom.2017.05.006","volume":"21","author":"JM Santos","year":"2017","unstructured":"Santos, J. M. et al. Red blood cell invasion by the malaria parasite is coordinated by the PfAP2-I transcription factor. Cell. Host. Microb. 21(6), 731-741.e10. https:\/\/doi.org\/10.1016\/j.chom.2017.05.006 (2017).","journal-title":"Cell. Host. Microb."},{"key":"3586_CR58","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.618454","volume":"10","author":"T Hollin","year":"2020","unstructured":"Hollin, T. & Le Roch, K. G. From genes to transcripts, a tightly regulated journey in Plasmodium. Front. Cell. Infect. Microbiol. 10, 618454. https:\/\/doi.org\/10.3389\/fcimb.2020.618454 (2020).","journal-title":"Front. Cell. Infect. Microbiol."},{"issue":"9","key":"3586_CR59","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1007329","volume":"15","author":"DF Read","year":"2019","unstructured":"Read, D. F., Cook, K., Lu, Y. Y., Le Roch, K. G. & Noble, W. S. Predicting gene expression in the human malaria parasite Plasmodium falciparum using histone modification, nucleosome positioning, and 3D localization features. PLoS Comput. Biol. 15(9), e1007329. https:\/\/doi.org\/10.1371\/journal.pcbi.1007329 (2019).","journal-title":"PLoS Comput. Biol."},{"issue":"10","key":"3586_CR60","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0013653","volume":"5","author":"S Helm","year":"2010","unstructured":"Helm, S. et al. Identification and characterization of a liver stage-specific promoter region of the malaria parasite Plasmodium. PLoS ONE 5(10), e13653. https:\/\/doi.org\/10.1371\/journal.pone.0013653 (2010).","journal-title":"PLoS ONE"},{"issue":"1","key":"3586_CR61","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1038\/s41467-024-44967-z","volume":"15","author":"J-L Wang","year":"2024","unstructured":"Wang, J.-L. et al. The transcription factor AP2XI-2 is a key negative regulator of Toxoplasma gondii merogony. Nat. Commun. 15(1), 793. https:\/\/doi.org\/10.1038\/s41467-024-44967-z (2024).","journal-title":"Nat. Commun."},{"issue":"15","key":"3586_CR62","doi-asserted-by":"publisher","first-page":"3100","DOI":"10.1093\/nar\/24.15.3100","volume":"24","author":"Y Wang","year":"1996","unstructured":"Wang, Y. Role of TATA box sequence and orientation in determining RNA polymerase II\/III transcription specificity. Nucl. Acid. Res. 24(15), 3100\u20133106. https:\/\/doi.org\/10.1093\/nar\/24.15.3100 (1996).","journal-title":"Nucl. Acid. Res."},{"issue":"12","key":"3586_CR63","doi-asserted-by":"publisher","first-page":"R178","DOI":"10.1186\/gb-2008-9-12-r178","volume":"9","author":"K Brick","year":"2008","unstructured":"Brick, K., Watanabe, J. & Pizzi, E. Core promoters are predicted by their distinct physicochemical properties in the genome of Plasmodium falciparum. Genome Biol. 9(12), R178. https:\/\/doi.org\/10.1186\/gb-2008-9-12-r178 (2008).","journal-title":"Genome Biol."},{"issue":"10","key":"3586_CR64","doi-asserted-by":"publisher","first-page":"2463","DOI":"10.1016\/j.celrep.2016.02.025","volume":"14","author":"SH Adjalley","year":"2016","unstructured":"Adjalley, S. H., Chabbert, C. D., Klaus, B., Pelechano, V. & Steinmetz, L. M. Landscape and dynamics of transcription initiation in the malaria parasite Plasmodium falciparum. Cell Rep. 14(10), 2463\u20132475. https:\/\/doi.org\/10.1016\/j.celrep.2016.02.025 (2016).","journal-title":"Cell Rep."},{"issue":"5","key":"3586_CR65","doi-asserted-by":"publisher","first-page":"2110","DOI":"10.1093\/nar\/gkv1214","volume":"44","author":"PR Kensche","year":"2016","unstructured":"Kensche, P. R. et al. The nucleosome landscape of Plasmodium falciparum reveals chromatin architecture and dynamics of regulatory sequences. Nucl. Acid. Res. 44(5), 2110\u20132124. https:\/\/doi.org\/10.1093\/nar\/gkv1214 (2016).","journal-title":"Nucl. Acid. Res."},{"key":"3586_CR66","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2020.111312","volume":"239","author":"O Parra-Mar\u00edn","year":"2020","unstructured":"Parra-Mar\u00edn, O., L\u00f3pez-Pacheco, K., Hern\u00e1ndez, R. & L\u00f3pez-Villase\u00f1or, I. The highly diverse TATA box-binding proteins among protists: A review. Mol. Biochem. Parasitol. 239, 111312. https:\/\/doi.org\/10.1016\/j.molbiopara.2020.111312 (2020).","journal-title":"Mol. Biochem. Parasitol."},{"key":"3586_CR67","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.11983","volume":"9","author":"PJ Shaw","year":"2021","unstructured":"Shaw, P. J. et al. Identifying transcript 5\u2032 capped ends in Plasmodium falciparum. PeerJ 9, e11983. https:\/\/doi.org\/10.7717\/peerj.11983 (2021).","journal-title":"PeerJ"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-03586-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-03586-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-03586-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T07:47:24Z","timestamp":1748418444000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-03586-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,28]]},"references-count":67,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["3586"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-03586-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,28]]},"assertion":[{"value":"2 September 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 May 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 May 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"18621"}}