{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T21:31:51Z","timestamp":1773869511629,"version":"3.50.1"},"reference-count":57,"publisher":"Proceedings of the National Academy of Sciences","issue":"52","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,12,26]]},"abstract":"<jats:p>\n            <jats:italic>Plasmodium falciparum<\/jats:italic>\n            causes the deadliest form of human malaria. Its virulence is attributed to its ability to modify the infected RBC and to evade human immune attack through antigenic variation. Antigenic variation is achieved through tight regulation of antigenic switches between variable surface antigens named \u201c\n            <jats:italic>P. falciparum<\/jats:italic>\n            erythrocyte membrane protein-1\u201d encoded by the\n            <jats:italic>var<\/jats:italic>\n            multicopy gene family. Individual parasites express only a single\n            <jats:italic>var<\/jats:italic>\n            gene at a time, maintaining the remaining\n            <jats:italic>var<\/jats:italic>\n            genes in a transcriptionally silent state. Strict pairing between\n            <jats:italic>var<\/jats:italic>\n            gene promoters and a second promoter within an intron found in each\n            <jats:italic>var<\/jats:italic>\n            gene is required for silencing and counting of\n            <jats:italic>var<\/jats:italic>\n            genes by the mechanism that controls mutually exclusive expression. We have identified and characterized insulator-like DNA elements that are required for pairing\n            <jats:italic>var<\/jats:italic>\n            promoters and introns and thus are essential for regulating silencing and mutually exclusive expression. These elements, found in the regulatory regions of each\n            <jats:italic>var<\/jats:italic>\n            gene, are bound by distinct nuclear protein complexes. Any alteration in the specific, paired structure of these elements by either deletion or insertion of additional elements results in an unregulated\n            <jats:italic>var<\/jats:italic>\n            gene. We propose a model by which silencing and mutually exclusive expression of\n            <jats:italic>var<\/jats:italic>\n            genes is regulated by the precise arrangement of insulator-like DNA pairing elements.\n          <\/jats:p>","DOI":"10.1073\/pnas.1214572109","type":"journal-article","created":{"date-parts":[[2012,11,30]],"date-time":"2012-11-30T07:02:42Z","timestamp":1354258962000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":34,"title":["Insulator-like pairing elements regulate silencing and mutually exclusive expression in the malaria parasite\n            <i>Plasmodium falciparum<\/i>"],"prefix":"10.1073","volume":"109","author":[{"given":"Inbar","family":"Avraham","sequence":"first","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, and"},{"name":"The Kuvin Center for the Study of Infectious and Tropical Diseases, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel"}]},{"given":"Jeremy","family":"Schreier","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, and"},{"name":"The Kuvin Center for the Study of Infectious and Tropical Diseases, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel"}]},{"given":"Ron","family":"Dzikowski","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, and"},{"name":"The Kuvin Center for the Study of Infectious and Tropical Diseases, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel"}]}],"member":"341","published-online":{"date-parts":[[2012,11,29]]},"reference":[{"key":"e_1_1_2_17_8_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2006.05.007"},{"key":"e_1_1_2_17_8_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/415673a"},{"key":"e_1_1_2_17_8_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/35091146"},{"key":"e_1_1_2_17_8_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00294-009-0233-2"},{"key":"e_1_1_2_17_8_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00329-10"},{"key":"e_1_3_3_1_2","unstructured":"; WHO World Malaria Report 2010. 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