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HC assembly involves three distinct steps:\n                    <jats:italic>de novo<\/jats:italic>\n                    nucleation, spreading and maintenance. Nucleation, which consists in formation of HC in a previously euchromatic region, determines the specific genomic locations where HC occurs. This process is not well understood in malaria parasites. Here we investigated the DNA sequence\n                    <jats:italic>cis<\/jats:italic>\n                    determinants of HC nucleation in\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    , using a screening approach based on integration of fragments from different heterochromatic genes into an euchromatic locus, followed by H3K9me3 chromatin immunoprecipitation (ChIP) analysis. We found that fragments of\n                    <jats:italic>var<\/jats:italic>\n                    gene upstream regions nucleated HC efficiently, whereas fragments from the\n                    <jats:italic>pfap2-g<\/jats:italic>\n                    upstream region or from the\n                    <jats:italic>mspdbl2<\/jats:italic>\n                    locus did not nucleate HC. Fragments from the beginning of the coding sequence (CDS) of\n                    <jats:italic>pfap2-g<\/jats:italic>\n                    nucleated HC with low efficiency, as evidenced by nucleation requiring long fragments of ~2 kb and occurring only in a fraction of the parasites. These results demonstrate that the primary DNA sequence is a main determinant of HC nucleation in\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    . We also studied HC maintenance at the\n                    <jats:italic>pfap2-g<\/jats:italic>\n                    locus, which demonstrated that specific parts of the upstream region, different from the regions competent for HC nucleation, are required for maintenance. Together, our results provide initial insight into how HC is directed to specific loci and maintained in\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013137","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T13:40:26Z","timestamp":1748871626000},"page":"e1013137","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Heterochromatin de novo formation and maintenance in Plasmodium falciparum"],"prefix":"10.1371","volume":"21","author":[{"given":"Alba","family":"P\u00e9rez-Cantero","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oriol","family":"Llor\u00e0-Batlle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Pelaez-Conde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9sar","family":"Mart\u00ednez-Guardiola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0730-6582","authenticated-orcid":true,"given":"Alfred","family":"Cort\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,6,2]]},"reference":[{"issue":"4","key":"ppat.1013137.ref001","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1038\/nrm.2017.119","article-title":"Ten 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Wang","year":"2016","journal-title":"Trends Genet"},{"issue":"10","key":"ppat.1013137.ref005","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1038\/nsmb.2382","article-title":"A transcription factor-based mechanism for mouse heterochromatin formation","volume":"19","author":"A Bulut-Karslioglu","year":"2012","journal-title":"Nat Struct Mol Biol"},{"issue":"1","key":"ppat.1013137.ref006","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1038\/s41467-022-29360-y","article-title":"DNA sequence-dependent formation of heterochromatin nanodomains","volume":"13","author":"GJ Thorn","year":"2022","journal-title":"Nat Commun"},{"issue":"7","key":"ppat.1013137.ref007","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/j.cell.2011.05.029","article-title":"Inheritance of stress-induced, ATF-2-dependent epigenetic change","volume":"145","author":"K-H 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Rovira-Graells","year":"2012","journal-title":"Genome Res"},{"issue":"2","key":"ppat.1013137.ref020","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":"VM Crowley","year":"2011","journal-title":"Mol Microbiol"},{"issue":"5","key":"ppat.1013137.ref021","doi-asserted-by":"crossref","first-page":"2224","DOI":"10.1073\/pnas.0913396107","article-title":"Epigenetic control of the variable expression of a Plasmodium falciparum receptor protein for erythrocyte invasion","volume":"107","author":"L Jiang","year":"2010","journal-title":"Proc Natl Acad Sci USA"},{"issue":"6","key":"ppat.1013137.ref022","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1111\/j.1365-2958.2007.06009.x","article-title":"5\u2019 flanking region of var genes nucleate histone modification patterns linked to phenotypic inheritance of virulence traits in malaria parasites","volume":"66","author":"JJ Lopez-Rubio","year":"2007","journal-title":"Mol Microbiol"},{"issue":"12","key":"ppat.1013137.ref023","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1002943","article-title":"A view on the role of epigenetics in the biology of malaria parasites","volume":"8","author":"A Cort\u00e9s","year":"2012","journal-title":"PLoS Pathog"},{"issue":"7","key":"ppat.1013137.ref024","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a025528","article-title":"Malaria Epigenetics","volume":"7","author":"A Cort\u00e9s","year":"2017","journal-title":"Cold Spring Harb Perspect Med"},{"key":"ppat.1013137.ref025","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":"TS Voss","year":"2014","journal-title":"Curr Opin Microbiol"},{"issue":"5","key":"ppat.1013137.ref026","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1093\/bfgp\/elz009","article-title":"Transcriptional variation in malaria parasites: why and how","volume":"18","author":"O Llor\u00e0-Batlle","year":"2019","journal-title":"Brief Funct Genomics"},{"issue":"2","key":"ppat.1013137.ref027","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.mib.2010.12.004","article-title":"Epigenetic switches: can infidelity govern fate in microbes?","volume":"14","author":"D Satory","year":"2011","journal-title":"Curr Opin Microbiol"},{"issue":"3","key":"ppat.1013137.ref028","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1111\/j.1469-185X.2012.00225.x","article-title":"Bet-hedging--a triple trade-off between means, variances and correlations","volume":"87","author":"J Starrfelt","year":"2012","journal-title":"Biol Rev Camb Philos 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Carrington","year":"2021","journal-title":"iScience"},{"issue":"6","key":"ppat.1013137.ref038","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":"X Shang","year":"2022","journal-title":"Nucleic Acids Res"},{"issue":"7491","key":"ppat.1013137.ref039","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":"BFC Kafsack","year":"2014","journal-title":"Nature"},{"issue":"11","key":"ppat.1013137.ref040","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1002992","article-title":"Population genomic scan for candidate signatures of balancing selection to guide antigen characterization in malaria 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