{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T18:43:09Z","timestamp":1771008189357,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,10,27]],"date-time":"2006-10-27T00:00:00Z","timestamp":1161907200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2007,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Alpha haemoglobin stabilising protein (AHSP) binds free <jats:italic>\u03b1<\/jats:italic>\u2010globin chains and plays an important role in the protection of red cells, particularly during <jats:italic>\u03b2<\/jats:italic>\u2010thalassaemia. Murine ASHP was discovered as a GATA\u20101 target gene and human AHSP is directly regulated by GATA\u20101. More recently, AHSP was rediscovered as a highly erythroid Kruppel\u2010like factor (EKLF) \u2010dependent transcript. We have determined the organisation of the murine AHSP gene and compared it to orthologs. There are two CACC box elements in the proximal promoter. The proximal element is absolutely conserved, but does not bind EKLF as it is not a canonical binding site. In rodents, the distal element contains a 3\u2003bp insertion that disrupts the typical EKLF binding consensus region. Nevertheless, EKLF binds this atypical site by gel mobility shift assay, specifically occupies the AHSP promoter <jats:italic>in vivo<\/jats:italic> in a chromatin immunoprecipitation assay, and transactivates AHSP through this CACC site in promoter\u2013reporter assays. Our results suggest EKLF can occupy CACC elements <jats:italic>in vivo<\/jats:italic> that are not predictable from the consensus binding site inferred from structural studies. We also propose that absence of AHSP in EKLF\u2010null red cells exacerbates the toxicity of free <jats:italic>\u03b1<\/jats:italic>\u2010globin chains, which exist because of the defect in <jats:italic>\u03b2<\/jats:italic>\u2010globin gene activation.<\/jats:p>","DOI":"10.1111\/j.1365-2141.2006.06381.x","type":"journal-article","created":{"date-parts":[[2006,10,27]],"date-time":"2006-10-27T11:40:43Z","timestamp":1161949243000},"page":"150-157","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Genomic organisation and regulation of murine alpha haemoglobin stabilising protein by erythroid Kruppel\u2010like factor"],"prefix":"10.1111","volume":"136","author":[{"given":"Janelle R.","family":"Keys","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael R.","family":"Tallack","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denise J.","family":"Hodge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon O.","family":"Cridland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rakesh","family":"David","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew C.","family":"Perkins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,10,27]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)42195-8"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.23.14347"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.6.1861"},{"key":"e_1_2_6_5_1","doi-asserted-by":"crossref","first-page":"15440","DOI":"10.1016\/S0021-9258(17)40698-3","article-title":"Regulation of the erythroid Kruppel\u2010like factor (EKLF) gene promoter by the erythroid transcription factor GATA\u20101","volume":"269","author":"Crossley M.","year":"1994","journal-title":"Journal of Biological Chemistry"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.4.1955"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.12.5205-5214.2005"},{"key":"e_1_2_6_8_1","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1016\/S0021-9258(17)42283-6","article-title":"Analyses of beta\u2010thalassaemia mutant DNA interactions with erythroid Kruppel\u2010like factor (EKLF), an erythroid cell\u2010specific transcription factor","volume":"269","author":"Feng W.C.","year":"1994","journal-title":"Journal of Biological Chemistry"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03609"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M506062200"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbaexp.2005.03.004"},{"key":"e_1_2_6_12_1","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1182\/blood.V87.5.1793.1793","article-title":"Functional interaction of GATA1 with erythroid Kruppel\u2010like factor and Sp1 at defined erythroid promoters","volume":"87","author":"Gregory R.C.","year":"1996","journal-title":"Blood"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-07-2888"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature00803"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI21982"},{"key":"e_1_2_6_16_1","doi-asserted-by":"crossref","first-page":"2054","DOI":"10.1182\/blood.V77.9.2054.2054","article-title":"Thalassaemia intermedia: moderate reduction of beta globin gene transcriptional activity by a novel mutation of the proximal CACCC promoter element","volume":"77","author":"Kulozik A.E.","year":"1991","journal-title":"Blood"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2006.06075.x"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh383"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.13.7.3999"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.13.5.2776"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2006.02.018"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/375316a0"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi048438p"},{"key":"e_1_2_6_24_1","doi-asserted-by":"crossref","first-page":"8679","DOI":"10.1016\/S0021-9258(17)47203-6","article-title":"Base substitution at position\u201088 in a beta\u2010thalassemic globin gene. 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