{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T05:36:40Z","timestamp":1777873000958,"version":"3.51.4"},"reference-count":36,"publisher":"Frontiers Media SA","issue":"7","license":[{"start":{"date-parts":[[2016,3,4]],"date-time":"2016-03-04T00:00:00Z","timestamp":1457049600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Exp Biol Med (Maywood)"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:p>\n                    Fetal hemoglobin is a major genetic modifier of the phenotypic heterogeneity in patients with sickle cell disease and certain \u03b2-thalassemias. Normal levels of fetal hemoglobin postnatally are approximately 1% of total hemoglobin. Patients who have hereditary persistence of fetal hemoglobin, characterized by elevated synthesis of \u03b3-globin in adulthood, show reduced disease pathophysiology. Hereditary persistence of fetal hemoglobin is caused by \u03b2-globin locus deletions (deletional hereditary persistence of fetal hemoglobin) or \u03b3-globin gene promoter point mutations (non-deletional hereditary persistence of fetal hemoglobin). Current research has focused on elucidating the pathways involved in the maintenance\/reactivation of \u03b3-globin in adult life. To better understand these pathways, we generated new \u03b2-globin locus yeast artificial chromosome transgenic mice bearing the\n                    <jats:sup>A<\/jats:sup>\n                    \u03b3-globin -175 T\u2009&gt;\u2009C or -195 C\u2009&gt;\u2009G hereditary persistence of fetal hemoglobin mutations to model naturally occurring hereditary persistence of fetal hemoglobin. Adult -175 and -195 mutant \u03b2-YAC mice displayed a hereditary persistence of fetal hemoglobin phenotype, as measured at the mRNA and protein levels. The molecular basis for these phenotypes was examined by chromatin immunoprecipitation of transcription factor\/co-factor binding, including YY1, PAX1, TAL1, LMO2, and LDB1. In -175 HPFH versus wild-type samples, the occupancy of LMO2, TAL1 and LDB1 proteins was enriched in HPFH mice (5.8-fold, 5.2-fold and 2.7-fold, respectively), a result that concurs with a recent study in cell lines showing that these proteins form a complex with GATA-1 to mediate long-range interactions between the locus control region and the\n                    <jats:sup>A<\/jats:sup>\n                    \u03b3-globin gene. Both hereditary persistence of fetal hemoglobin mutations result in a gain of\n                    <jats:sup>A<\/jats:sup>\n                    \u03b3-globin activation, in contrast to other hereditary persistence of fetal hemoglobin mutations that result in a loss of repression. The mice provide additional tools to study \u03b3-globin gene expression and may reveal new targets for selectively activating fetal hemoglobin.\n                  <\/jats:p>","DOI":"10.1177\/1535370216636724","type":"journal-article","created":{"date-parts":[[2016,3,5]],"date-time":"2016-03-05T20:08:18Z","timestamp":1457208498000},"page":"697-705","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Original Research: Generation of non-deletional hereditary persistence of fetal hemoglobin \u03b2-globin locus yeast artificial chromosome transgenic mouse models: -175 Black HPFH and -195 Brazilian HPFH"],"prefix":"10.3389","volume":"241","author":[{"given":"Carolina A","family":"Braghini","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS 66160 USA"},{"name":"Hematology and Hemotherapy Center, University of Campinas, Sao Paulo, SP 13083, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flavia C","family":"Costa","sequence":"additional","affiliation":[{"name":"IntelligeneDX, Olathe, KS 66061, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Halyna","family":"Fedosyuk","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS 66160 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renee Y","family":"Neades","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS 66160 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lesya V","family":"Novikova","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS 66160 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