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dc.contributor.authorZhu, Xingguo
dc.contributor.authorWang, Yongchao
dc.contributor.authorPi, Wenhu
dc.contributor.authorLiu, Hui
dc.contributor.authorWickrema, Amittha
dc.contributor.authorTuan, Dorothy
dc.date.accessioned2012-10-26T20:35:13Z
dc.date.available2012-10-26T20:35:13Z
dc.date.issued2012-10-10en_US
dc.identifier.citationPLoS One. 2012 Oct 10; 7(10):e47175en_US
dc.identifier.issn1932-6203en_US
dc.identifier.pmid23071749en_US
dc.identifier.doi10.1371/journal.pone.0047175en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/831
dc.description.abstractThe human embryonic, fetal and adult β-like globin genes provide a paradigm for tissue- and developmental stage-specific gene regulation. The fetal γ-globin gene is expressed in fetal erythroid cells but is repressed in adult erythroid cells. The molecular mechanism underlying this transcriptional switch during erythroid development is not completely understood. Here, we used a combination of in vitro and in vivo assays to dissect the molecular assemblies of the active and the repressed proximal γ-globin promoter complexes in K562 human erythroleukemia cell line and primary human fetal and adult erythroid cells. We found that the proximal γ-globin promoter complex is assembled by a developmentally regulated, general transcription activator NF-Y bound strongly at the tandem CCAAT motifs near the TATA box. NF-Y recruits to neighboring DNA motifs the developmentally regulated, erythroid transcription activator GATA-2 and general repressor BCL11A, which in turn recruit erythroid repressor GATA-1 and general repressor COUP-TFII to form respectively the NF-Y/GATA-2 transcription activator hub and the BCL11A/COUP-TFII/GATA-1 transcription repressor hub. Both the activator and the repressor hubs are present in both the active and the repressed γ-globin promoter complexes in fetal and adult erythroid cells. Through changes in their levels and respective interactions with the co-activators and co-repressors during erythroid development, the activator and the repressor hubs modulate erythroid- and developmental stage-specific transcription of γ-globin gene.
dc.subjectResearch Articleen_US
dc.subjectBiologyen_US
dc.subjectBiochemistryen_US
dc.subjectNucleic Acidsen_US
dc.subjectDNAen_US
dc.subjectRNAen_US
dc.subjectMacromolecular Assembliesen_US
dc.subjectDevelopmental Biologyen_US
dc.subjectMolecular Developmenten_US
dc.subjectGeneticsen_US
dc.subjectMolecular Geneticsen_US
dc.subjectGene Regulationen_US
dc.subjectMolecular Cell Biologyen_US
dc.subjectGene Expressionen_US
dc.subjectDNA transcriptionen_US
dc.subjectNucleic Acidsen_US
dc.subjectDNAen_US
dc.subjectRNAen_US
dc.subjectMedicineen_US
dc.subjectHematologyen_US
dc.subjectHemoglobinopathiesen_US
dc.subjectSickle Cell Diseaseen_US
dc.subjectBeta-Thalassemiaen_US
dc.subjectHematopoiesisen_US
dc.subjectRed Cellsen_US
dc.titleNF-Y Recruits Both Transcription Activator and Repressor to Modulate Tissue- and Developmental Stage-Specific Expression of Human γ-Globin Geneen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3468502en_US
dc.contributor.corporatenameDepartment of Biochemistry and Molecular Biology
refterms.dateFOA2019-04-10T00:58:40Z
html.description.abstractThe human embryonic, fetal and adult β-like globin genes provide a paradigm for tissue- and developmental stage-specific gene regulation. The fetal γ-globin gene is expressed in fetal erythroid cells but is repressed in adult erythroid cells. The molecular mechanism underlying this transcriptional switch during erythroid development is not completely understood. Here, we used a combination of in vitro and in vivo assays to dissect the molecular assemblies of the active and the repressed proximal γ-globin promoter complexes in K562 human erythroleukemia cell line and primary human fetal and adult erythroid cells. We found that the proximal γ-globin promoter complex is assembled by a developmentally regulated, general transcription activator NF-Y bound strongly at the tandem CCAAT motifs near the TATA box. NF-Y recruits to neighboring DNA motifs the developmentally regulated, erythroid transcription activator GATA-2 and general repressor BCL11A, which in turn recruit erythroid repressor GATA-1 and general repressor COUP-TFII to form respectively the NF-Y/GATA-2 transcription activator hub and the BCL11A/COUP-TFII/GATA-1 transcription repressor hub. Both the activator and the repressor hubs are present in both the active and the repressed γ-globin promoter complexes in fetal and adult erythroid cells. Through changes in their levels and respective interactions with the co-activators and co-repressors during erythroid development, the activator and the repressor hubs modulate erythroid- and developmental stage-specific transcription of γ-globin gene.


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