Identificador persistente para citar o vincular este elemento: http://hdl.handle.net/10553/49987
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dc.contributor.authorMagness, Scott T.en_US
dc.contributor.authorTugores, Antonioen_US
dc.contributor.authorBrenner, David A.en_US
dc.date.accessioned2018-11-24T12:21:15Z-
dc.date.available2018-11-24T12:21:15Z-
dc.date.issued2000en_US
dc.identifier.issn0006-4971en_US
dc.identifier.urihttp://hdl.handle.net/10553/49987-
dc.description.abstractFerrochelatase, the last enzyme in the heme pathway, chelates protoporphyrin IX and iron to form heme and is mutated in protoporphyria. The ferrochelatase gene is expressed in all tissues at low levels to provide heme for essential heme-containing proteins and is up-regulated during erythropoiesis for the synthesis of hemoglobin. The human ferrochelatase promoter contains 2 Sp1 cis-elements and GATA and NF–E2 sites, all of which bind their cognatetrans-acting factors in vitro. To investigate the role of these elements during erythropoiesis, we introduced expression of the green fluorescent protein (EGFP) transgenes driven by various ferrochelatase promoter fragments into a single locus in mouse embryonic stem cells. EGFP expression was monitored during hematopoietic differentiation in vitro using flow cytometry. We show that a promoter fragment containing the Sp1 sites, the NF–E2 and GATA elements, was sufficient to confer developmental-specific expression of the EGFP transgene, with an expression profile identical to that of the endogenous gene. In this system the −0.275 kb NF–E2 cis-element is required for erythroid-enhanced expression, the GATA cis-element functions as a stage-specific repressor and enhancer, and elements located between −0.375kb and −1.1kb are necessary for optimal levels of expression. Ferrochelatase mRNA increased before the primitive erythroid-cell stage without a concomitant increase in ferrochelatase protein, suggesting the presence of a translational control mechanism. Because of the sensitivity of this system, we were able to assess the effect of an A-to-G polymorphism identified in the promoters of patients with protoporphyria. There was no effect of the G haplotype on transcriptional activity of the −1.1 kb transgene.en_US
dc.languageengen_US
dc.relation.ispartofBlooden_US
dc.sourceBlood[ISSN 0006-4971],v. 95, p. 3568-3577en_US
dc.subject32 Ciencias médicasen_US
dc.subject320504 Hematologíaen_US
dc.subject.otherFerrochelataseen_US
dc.subject.otherHematopoiesisen_US
dc.subject.otherStem cellsen_US
dc.titleAnalysis of ferrochelatase expression during hematopoietic development of embryonic stem cellsen_US
dc.typeinfo:eu-repo/semantics/articleen_US
dc.typeArticleen_US
dc.identifier.doi10.1182/blood.V95.11.3568en_US
dc.identifier.scopus0034210967-
dc.contributor.authorscopusid6603642454-
dc.contributor.authorscopusid6701671839-
dc.contributor.authorscopusid7201995762-
dc.description.lastpage3577en_US
dc.description.firstpage3568en_US
dc.relation.volume95en_US
dc.investigacionCiencias de la Saluden_US
dc.type2Artículoen_US
dc.description.numberofpages10en_US
dc.utils.revisionen_US
dc.date.coverdateJunio 2000en_US
dc.identifier.ulpgcen_US
dc.contributor.buulpgcBU-MEDen_US
dc.description.jcr8,977-
dc.description.jcrqQ1-
dc.description.scieSCIE-
item.fulltextSin texto completo-
item.grantfulltextnone-
crisitem.author.deptGIR IUIBS: Diabetes y endocrinología aplicada-
crisitem.author.deptIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.orcid0000-0002-1849-9239-
crisitem.author.parentorgIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.fullNameTugores Céster,Antonio-
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