{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:07:58Z","timestamp":1781104078846,"version":"3.54.1"},"reference-count":47,"publisher":"National Academy of Sciences","issue":"26","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,12,19]]},"abstract":"<jats:p>Developmental expression at the \u03b2-globin locus is regulated\n in part by the locus control region, a region upstream of the genes\n containing at least five major DNase I hypersensitive sites (HSs) in\n mammalian erythrocytes. Sequences farther 5\u2032 of these HSs are conserved\n in mouse and human, and both loci are embedded within a cluster of\n functional odorant receptor genes. In humans, distant upstream\n sequences have been implicated in regulation of the \u03b2-globin genes.\n In this study, the role of the 5\u2032-most HSs and their adjacent sequence\n was investigated by deletion of an 11-kb region from the mouse locus,\n including 5\u2032HS 4.2, 5\u2032HS 5, 5\u2032HS 6, and the 5\u2032\u03b21 odorant receptor\n gene. Mice that were homozygous for this deletion were fully viable,\n and no significant effect on adult \u03b2-globin gene expression was seen.\n 5\u2032HSs 1\u20134, which are located downstream of the deletion, were still\n present in the mutant mice. In addition, two new upstream HSs, HS\n \u221260.7 and HS \u221262.5, were found in erythroid tissue of both wild-type\n and mutant mice. Therefore, although the possibility of a minor role\n still exists, neither the HSs nor the other regions deleted in this\n study are essential for \u03b2-globin gene expression, and it is unlikely\n that chromatin structure is affected either upstream or downstream of\n the deletion. This is the largest deletion at the mouse locus control\n region to show no apparent phenotype, and focuses attention on the\n possible contribution of sequences even farther upstream.<\/jats:p>","DOI":"10.1073\/pnas.97.26.14554","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:44:19Z","timestamp":1027680259000},"page":"14554-14559","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":32,"title":["A large upstream region is not necessary for gene expression or hypersensitive site formation at the mouse \u03b2-globin locus"],"prefix":"10.1073","volume":"97","author":[{"given":"Catherine M.","family":"Farrell","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Biology, National Institute of Diabetes\r and Digestive Kidney Diseases, National Institutes of Health, Bethesda,\r MD 20892-0540; and Laboratory of Mammalian Genes and\r Development, National Institute of Child Health and Human Development,\r National Institutes of Health, Bethesda, MD 20892-2790"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Grinberg","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, National Institute of Diabetes\r and Digestive Kidney Diseases, National Institutes of Health, Bethesda,\r MD 20892-0540; and Laboratory of Mammalian Genes and\r Development, National Institute of Child Health and Human Development,\r National Institutes of Health, Bethesda, MD 20892-2790"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sing Ping","family":"Huang","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, National Institute of Diabetes\r and Digestive Kidney Diseases, National Institutes of Health, Bethesda,\r MD 20892-0540; and Laboratory of Mammalian Genes and\r Development, National Institute of Child Health and Human Development,\r National Institutes of Health, Bethesda, MD 20892-2790"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Chen","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, National Institute of Diabetes\r and Digestive Kidney Diseases, National Institutes of Health, Bethesda,\r MD 20892-0540; and Laboratory of Mammalian Genes and\r Development, National Institute of Child Health and Human Development,\r National Institutes of Health, Bethesda, MD 20892-2790"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 G.","family":"Pichel","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, National Institute of Diabetes\r and Digestive Kidney Diseases, National Institutes of Health, Bethesda,\r MD 20892-0540; 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