{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T22:21:32Z","timestamp":1770502892848,"version":"3.49.0"},"reference-count":34,"publisher":"Proceedings of the National Academy of Sciences","issue":"20","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,9,25]]},"abstract":"<jats:p>\n            Locus control regions (LCRs) are defined by their ability to confer\n high-level tissue-specific expression to linked genes in transgenic\n assays. Previously, we reported that, at its native site, the murine\n \u03b2-globin LCR is required for high-level \u03b2-globin gene expression,\n but is not required to initiate an open chromatin conformation of the\n locus. To further investigate the mechanism of LCR-mediated\n transcriptional enhancement, we have analyzed allele-specific\n \u03b2-globin expression and the pattern of histone acetylation in the\n presence and absence of the LCR. In single cells from mice heterozygous\n for a deletion of the LCR, \u03b2-globin expression from the LCR-deleted\n allele is consistently low (\u22481\u20134% of wild type). Thus, the\n endogenous LCR enhances globin gene expression by\n increasing the rate of transcription from each linked allele rather\n than by increasing the probability of establishing transcription\n            <jats:italic>per se<\/jats:italic>\n            . Furthermore, in erythroid cells from mice\n homozygous for the highly expressing wild-type \u03b2-globin locus,\n hyperacetylation of histones H3 and H4 is localized to the LCR and\n active genes. In mice homozygous for the LCR deletion reduced histone\n hyperacetylation is observed in LCR proximal sequences; however,\n deletion of the LCR has no effect on the localized hyperacetylation of\n the genes. Together, our results suggest that, in its native genomic\n context, the LCR follows the rate model of enhancer function, and that\n the developmentally specific hyperacetylation of the globin genes is\n independent of both the rate of transcription and the presence of the\n LCR.\n          <\/jats:p>","DOI":"10.1073\/pnas.201394698","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T14:34:10Z","timestamp":1027694050000},"page":"11432-11437","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":77,"title":["The murine \u03b2-globin locus control region regulates the rate of transcription but not the hyperacetylation of histones at the active genes"],"prefix":"10.1073","volume":"98","author":[{"given":"Dirk","family":"Sch\u00fcbeler","sequence":"first","affiliation":[{"name":"Fred Hutchinson Cancer Research Center, Seattle, WA 98109; and\r Departments of Radiation Oncology and\r Pediatrics, University of Washington School of\r Medicine, Seattle, WA 98195"}]},{"given":"Mark","family":"Groudine","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Research Center, Seattle, WA 98109; and\r Departments of Radiation Oncology and\r Pediatrics, University of Washington School of\r Medicine, Seattle, WA 98195"}]},{"given":"M. A.","family":"Bender","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Research Center, Seattle, WA 98109; and\r Departments of Radiation Oncology and\r Pediatrics, University of Washington School of\r Medicine, Seattle, WA 98195"}]}],"member":"341","published-online":{"date-parts":[[2001,9,11]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.19.2465"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80686-8"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81761-4"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80144-6"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.18.10.5992"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80433-5"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-1878(200004)22:4<381::AID-BIES8>3.0.CO;2-E"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81657-8"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.9.2969-2980.2001"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80054-9"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80181-1"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.14.8.940"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80740-0"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00169-0"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.11.1412"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00188-4"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.24.6814"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.9.2224"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.287.5452.495"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.26.14494"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V92.11.4394.423k48_4394_4403"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.9.18.2203"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.13.7.3990-3998.1993"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.5.599"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/47412"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.23.11381"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80073-2"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1994.tb06451.x"},{"key":"e_1_3_3_29_2","first-page":"157","volume-title":"The Molecular Basis of Blood Diseases","author":"Weatherall D J","year":"1994","unstructured":"D J Weatherall The Molecular Basis of Blood Diseases, eds G Stamatoyannopoulos, A W Nienhus, P W Majerus, H Varmus (Saunders, Philadelphia), pp. 157\u2013206 (1994)."},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80251-4"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.10.7031"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.10.2.185"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.8.18.2212"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.18.11.6281"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.201394698","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T10:59:37Z","timestamp":1649847577000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.201394698"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,9,11]]},"references-count":34,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2001,9,25]]}},"alternative-id":["10.1073\/pnas.201394698"],"URL":"https:\/\/doi.org\/10.1073\/pnas.201394698","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,9,11]]},"assertion":[{"value":"2001-05-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2001-07-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2001-09-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}