PubMed:7721747 JSONTXT

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    sentences

    {"project":"sentences","denotations":[{"id":"T1","span":{"begin":0,"end":83},"obj":"Sentence"},{"id":"T2","span":{"begin":84,"end":140},"obj":"Sentence"},{"id":"T3","span":{"begin":141,"end":309},"obj":"Sentence"},{"id":"T4","span":{"begin":310,"end":511},"obj":"Sentence"},{"id":"T5","span":{"begin":512,"end":692},"obj":"Sentence"},{"id":"T6","span":{"begin":693,"end":936},"obj":"Sentence"},{"id":"T7","span":{"begin":937,"end":1241},"obj":"Sentence"},{"id":"T8","span":{"begin":1242,"end":1437},"obj":"Sentence"},{"id":"T9","span":{"begin":1438,"end":1516},"obj":"Sentence"},{"id":"T10","span":{"begin":1517,"end":1803},"obj":"Sentence"},{"id":"T1","span":{"begin":0,"end":83},"obj":"Sentence"},{"id":"T2","span":{"begin":84,"end":140},"obj":"Sentence"},{"id":"T3","span":{"begin":141,"end":309},"obj":"Sentence"},{"id":"T4","span":{"begin":310,"end":511},"obj":"Sentence"},{"id":"T5","span":{"begin":512,"end":692},"obj":"Sentence"},{"id":"T6","span":{"begin":693,"end":936},"obj":"Sentence"},{"id":"T7","span":{"begin":937,"end":1241},"obj":"Sentence"},{"id":"T8","span":{"begin":1242,"end":1437},"obj":"Sentence"},{"id":"T9","span":{"begin":1438,"end":1516},"obj":"Sentence"},{"id":"T10","span":{"begin":1517,"end":1803},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"Functional roles of in vivo footprinted DNA motifs within an alpha-globin enhancer. Erythroid lineage and developmental stage specificities.\nTranscriptional regulation of the human alpha-like globin genes, embryonic zeta 2 and adult alpha, during erythroid development is mediated by a distal enhancer, HS-40. Previous protein-DNA binding studies have shown that HS-40 consists of multiple nuclear factor binding motifs that are occupied in vivo in an erythroid lineage- and developmental stage-specific manner. We have systematically analyzed the functional roles of these factor binding motifs of HS-40 by site-directed mutagenesis and transient expression assay in erythroid cell cultures. Three of these HS-40 enhancer motifs, 5'NF-E2/AP1, GT II, and GATA-1(c), positively regulate the zeta 2-globin promoter activity in embryonic/fetal erythroid K562 cells and the adult alpha-globin promoter activity in adult erythroid MEL cells. On the other hand, the 3'NF-E2/AP1 motif is able to exert both positive and negative regulatory effects on the zeta 2-globin promoter activity in K562 cells, and this dual function appears to be modulated through differential binding of the ubiquitous AP1 factors and the erythroid-enriched NF-E2 factor. Mutation in the GATA-1(d) motif, which exhibits an adult erythroid-specific genomic footprint, decreases the HS-40 enhancer function in dimethyl sulfoxide-induced MEL cells but not in K562 cells. These studies have defined the regulatory roles of the different HS-40 motifs. The remarkable correlation between genomic footprinting data and the mutagenesis results also suggests that the erythroid lineage- and developmental stage-specific regulation of human alpha-like globin promoters is indeed modulated by stable binding of specific nuclear factors in vivo."}

    Glycosmos6-MAT

    {"project":"Glycosmos6-MAT","denotations":[{"id":"T1","span":{"begin":950,"end":954},"obj":"http://purl.obolibrary.org/obo/MAT_0000091"}],"text":"Functional roles of in vivo footprinted DNA motifs within an alpha-globin enhancer. Erythroid lineage and developmental stage specificities.\nTranscriptional regulation of the human alpha-like globin genes, embryonic zeta 2 and adult alpha, during erythroid development is mediated by a distal enhancer, HS-40. Previous protein-DNA binding studies have shown that HS-40 consists of multiple nuclear factor binding motifs that are occupied in vivo in an erythroid lineage- and developmental stage-specific manner. We have systematically analyzed the functional roles of these factor binding motifs of HS-40 by site-directed mutagenesis and transient expression assay in erythroid cell cultures. Three of these HS-40 enhancer motifs, 5'NF-E2/AP1, GT II, and GATA-1(c), positively regulate the zeta 2-globin promoter activity in embryonic/fetal erythroid K562 cells and the adult alpha-globin promoter activity in adult erythroid MEL cells. On the other hand, the 3'NF-E2/AP1 motif is able to exert both positive and negative regulatory effects on the zeta 2-globin promoter activity in K562 cells, and this dual function appears to be modulated through differential binding of the ubiquitous AP1 factors and the erythroid-enriched NF-E2 factor. Mutation in the GATA-1(d) motif, which exhibits an adult erythroid-specific genomic footprint, decreases the HS-40 enhancer function in dimethyl sulfoxide-induced MEL cells but not in K562 cells. These studies have defined the regulatory roles of the different HS-40 motifs. The remarkable correlation between genomic footprinting data and the mutagenesis results also suggests that the erythroid lineage- and developmental stage-specific regulation of human alpha-like globin promoters is indeed modulated by stable binding of specific nuclear factors in vivo."}

    jnlpba-st-training

    {"project":"jnlpba-st-training","denotations":[{"id":"T1","span":{"begin":20,"end":50},"obj":"DNA"},{"id":"T2","span":{"begin":61,"end":82},"obj":"DNA"},{"id":"T3","span":{"begin":175,"end":204},"obj":"DNA"},{"id":"T4","span":{"begin":206,"end":222},"obj":"DNA"},{"id":"T5","span":{"begin":227,"end":238},"obj":"DNA"},{"id":"T6","span":{"begin":286,"end":301},"obj":"DNA"},{"id":"T7","span":{"begin":303,"end":308},"obj":"DNA"},{"id":"T8","span":{"begin":363,"end":368},"obj":"DNA"},{"id":"T9","span":{"begin":390,"end":419},"obj":"DNA"},{"id":"T10","span":{"begin":574,"end":595},"obj":"DNA"},{"id":"T11","span":{"begin":599,"end":604},"obj":"DNA"},{"id":"T12","span":{"begin":668,"end":691},"obj":"cell_line"},{"id":"T13","span":{"begin":708,"end":729},"obj":"DNA"},{"id":"T14","span":{"begin":731,"end":742},"obj":"DNA"},{"id":"T15","span":{"begin":744,"end":749},"obj":"DNA"},{"id":"T16","span":{"begin":755,"end":764},"obj":"DNA"},{"id":"T17","span":{"begin":790,"end":812},"obj":"DNA"},{"id":"T18","span":{"begin":825,"end":861},"obj":"cell_line"},{"id":"T19","span":{"begin":870,"end":897},"obj":"DNA"},{"id":"T20","span":{"begin":910,"end":935},"obj":"cell_line"},{"id":"T21","span":{"begin":960,"end":977},"obj":"DNA"},{"id":"T22","span":{"begin":1048,"end":1070},"obj":"DNA"},{"id":"T23","span":{"begin":1083,"end":1093},"obj":"cell_line"},{"id":"T24","span":{"begin":1178,"end":1200},"obj":"protein"},{"id":"T25","span":{"begin":1209,"end":1240},"obj":"protein"},{"id":"T26","span":{"begin":1258,"end":1273},"obj":"DNA"},{"id":"T27","span":{"begin":1293,"end":1335},"obj":"DNA"},{"id":"T28","span":{"begin":1351,"end":1365},"obj":"DNA"},{"id":"T29","span":{"begin":1378,"end":1414},"obj":"cell_line"},{"id":"T30","span":{"begin":1426,"end":1436},"obj":"cell_line"},{"id":"T31","span":{"begin":1503,"end":1515},"obj":"DNA"},{"id":"T32","span":{"begin":1695,"end":1728},"obj":"DNA"},{"id":"T33","span":{"begin":1770,"end":1794},"obj":"protein"}],"text":"Functional roles of in vivo footprinted DNA motifs within an alpha-globin enhancer. Erythroid lineage and developmental stage specificities.\nTranscriptional regulation of the human alpha-like globin genes, embryonic zeta 2 and adult alpha, during erythroid development is mediated by a distal enhancer, HS-40. Previous protein-DNA binding studies have shown that HS-40 consists of multiple nuclear factor binding motifs that are occupied in vivo in an erythroid lineage- and developmental stage-specific manner. We have systematically analyzed the functional roles of these factor binding motifs of HS-40 by site-directed mutagenesis and transient expression assay in erythroid cell cultures. Three of these HS-40 enhancer motifs, 5'NF-E2/AP1, GT II, and GATA-1(c), positively regulate the zeta 2-globin promoter activity in embryonic/fetal erythroid K562 cells and the adult alpha-globin promoter activity in adult erythroid MEL cells. On the other hand, the 3'NF-E2/AP1 motif is able to exert both positive and negative regulatory effects on the zeta 2-globin promoter activity in K562 cells, and this dual function appears to be modulated through differential binding of the ubiquitous AP1 factors and the erythroid-enriched NF-E2 factor. Mutation in the GATA-1(d) motif, which exhibits an adult erythroid-specific genomic footprint, decreases the HS-40 enhancer function in dimethyl sulfoxide-induced MEL cells but not in K562 cells. These studies have defined the regulatory roles of the different HS-40 motifs. The remarkable correlation between genomic footprinting data and the mutagenesis results also suggests that the erythroid lineage- and developmental stage-specific regulation of human alpha-like globin promoters is indeed modulated by stable binding of specific nuclear factors in vivo."}

    genia-medco-coref

    {"project":"genia-medco-coref","denotations":[{"id":"C1","span":{"begin":58,"end":82},"obj":"NP"},{"id":"C2","span":{"begin":171,"end":204},"obj":"NP"},{"id":"C3","span":{"begin":206,"end":238},"obj":"NP"},{"id":"C4","span":{"begin":284,"end":301},"obj":"NP"},{"id":"C5","span":{"begin":303,"end":308},"obj":"NP"},{"id":"C6","span":{"begin":363,"end":368},"obj":"NP"},{"id":"C8","span":{"begin":381,"end":419},"obj":"NP"},{"id":"C9","span":{"begin":420,"end":424},"obj":"NP"},{"id":"C7","span":{"begin":381,"end":510},"obj":"NP"},{"id":"C11","span":{"begin":599,"end":604},"obj":"NP"},{"id":"C10","span":{"begin":568,"end":604},"obj":"NP"},{"id":"C13","span":{"begin":702,"end":729},"obj":"NP"},{"id":"C12","span":{"begin":693,"end":729},"obj":"NP"},{"id":"C14","span":{"begin":731,"end":764},"obj":"NP"},{"id":"C15","span":{"begin":786,"end":821},"obj":"NP"},{"id":"C16","span":{"begin":825,"end":861},"obj":"NP"},{"id":"C17","span":{"begin":1044,"end":1079},"obj":"NP"},{"id":"C18","span":{"begin":1083,"end":1093},"obj":"NP"},{"id":"C19","span":{"begin":1242,"end":1273},"obj":"NP"},{"id":"C20","span":{"begin":1275,"end":1280},"obj":"NP"},{"id":"C21","span":{"begin":1426,"end":1436},"obj":"NP"},{"id":"C22","span":{"begin":1489,"end":1515},"obj":"NP"}],"relations":[{"id":"R1","pred":"coref-appos","subj":"C3","obj":"C2"},{"id":"R2","pred":"coref-ident","subj":"C4","obj":"C1"},{"id":"R3","pred":"coref-appos","subj":"C5","obj":"C4"},{"id":"R4","pred":"coref-ident","subj":"C6","obj":"C5"},{"id":"R5","pred":"coref-relat","subj":"C9","obj":"C8"},{"id":"R6","pred":"coref-ident","subj":"C11","obj":"C6"},{"id":"R7","pred":"coref-ident","subj":"C10","obj":"C7"},{"id":"R8","pred":"coref-ident","subj":"C13","obj":"C10"},{"id":"R9","pred":"coref-appos","subj":"C14","obj":"C12"},{"id":"R10","pred":"coref-ident","subj":"C17","obj":"C15"},{"id":"R11","pred":"coref-ident","subj":"C18","obj":"C16"},{"id":"R12","pred":"coref-relat","subj":"C20","obj":"C19"},{"id":"R13","pred":"coref-ident","subj":"C21","obj":"C18"},{"id":"R14","pred":"coref-ident","subj":"C22","obj":"C10"}],"text":"Functional roles of in vivo footprinted DNA motifs within an alpha-globin enhancer. Erythroid lineage and developmental stage specificities.\nTranscriptional regulation of the human alpha-like globin genes, embryonic zeta 2 and adult alpha, during erythroid development is mediated by a distal enhancer, HS-40. Previous protein-DNA binding studies have shown that HS-40 consists of multiple nuclear factor binding motifs that are occupied in vivo in an erythroid lineage- and developmental stage-specific manner. We have systematically analyzed the functional roles of these factor binding motifs of HS-40 by site-directed mutagenesis and transient expression assay in erythroid cell cultures. Three of these HS-40 enhancer motifs, 5'NF-E2/AP1, GT II, and GATA-1(c), positively regulate the zeta 2-globin promoter activity in embryonic/fetal erythroid K562 cells and the adult alpha-globin promoter activity in adult erythroid MEL cells. On the other hand, the 3'NF-E2/AP1 motif is able to exert both positive and negative regulatory effects on the zeta 2-globin promoter activity in K562 cells, and this dual function appears to be modulated through differential binding of the ubiquitous AP1 factors and the erythroid-enriched NF-E2 factor. Mutation in the GATA-1(d) motif, which exhibits an adult erythroid-specific genomic footprint, decreases the HS-40 enhancer function in dimethyl sulfoxide-induced MEL cells but not in K562 cells. These studies have defined the regulatory roles of the different HS-40 motifs. The remarkable correlation between genomic footprinting data and the mutagenesis results also suggests that the erythroid lineage- and developmental stage-specific regulation of human alpha-like globin promoters is indeed modulated by stable binding of specific nuclear factors in vivo."}

    pubmed-sentences-benchmark

    {"project":"pubmed-sentences-benchmark","denotations":[{"id":"S1","span":{"begin":0,"end":83},"obj":"Sentence"},{"id":"S2","span":{"begin":84,"end":140},"obj":"Sentence"},{"id":"S3","span":{"begin":141,"end":309},"obj":"Sentence"},{"id":"S4","span":{"begin":310,"end":511},"obj":"Sentence"},{"id":"S5","span":{"begin":512,"end":692},"obj":"Sentence"},{"id":"S6","span":{"begin":693,"end":936},"obj":"Sentence"},{"id":"S7","span":{"begin":937,"end":1241},"obj":"Sentence"},{"id":"S8","span":{"begin":1242,"end":1437},"obj":"Sentence"},{"id":"S9","span":{"begin":1438,"end":1516},"obj":"Sentence"},{"id":"S10","span":{"begin":1517,"end":1803},"obj":"Sentence"}],"text":"Functional roles of in vivo footprinted DNA motifs within an alpha-globin enhancer. Erythroid lineage and developmental stage specificities.\nTranscriptional regulation of the human alpha-like globin genes, embryonic zeta 2 and adult alpha, during erythroid development is mediated by a distal enhancer, HS-40. Previous protein-DNA binding studies have shown that HS-40 consists of multiple nuclear factor binding motifs that are occupied in vivo in an erythroid lineage- and developmental stage-specific manner. We have systematically analyzed the functional roles of these factor binding motifs of HS-40 by site-directed mutagenesis and transient expression assay in erythroid cell cultures. Three of these HS-40 enhancer motifs, 5'NF-E2/AP1, GT II, and GATA-1(c), positively regulate the zeta 2-globin promoter activity in embryonic/fetal erythroid K562 cells and the adult alpha-globin promoter activity in adult erythroid MEL cells. On the other hand, the 3'NF-E2/AP1 motif is able to exert both positive and negative regulatory effects on the zeta 2-globin promoter activity in K562 cells, and this dual function appears to be modulated through differential binding of the ubiquitous AP1 factors and the erythroid-enriched NF-E2 factor. Mutation in the GATA-1(d) motif, which exhibits an adult erythroid-specific genomic footprint, decreases the HS-40 enhancer function in dimethyl sulfoxide-induced MEL cells but not in K562 cells. These studies have defined the regulatory roles of the different HS-40 motifs. The remarkable correlation between genomic footprinting data and the mutagenesis results also suggests that the erythroid lineage- and developmental stage-specific regulation of human alpha-like globin promoters is indeed modulated by stable binding of specific nuclear factors in vivo."}

    GENIAcorpus

    {"project":"GENIAcorpus","denotations":[{"id":"T1","span":{"begin":20,"end":50},"obj":"DNA_family_or_group"},{"id":"T2","span":{"begin":61,"end":82},"obj":"DNA_domain_or_region"},{"id":"T3","span":{"begin":84,"end":101},"obj":"other_name"},{"id":"T4","span":{"begin":141,"end":167},"obj":"other_name"},{"id":"T5","span":{"begin":175,"end":204},"obj":"DNA_family_or_group"},{"id":"T6","span":{"begin":206,"end":222},"obj":"DNA_domain_or_region"},{"id":"T7","span":{"begin":227,"end":238},"obj":"DNA_domain_or_region"},{"id":"T8","span":{"begin":247,"end":268},"obj":"other_name"},{"id":"T9","span":{"begin":286,"end":301},"obj":"DNA_domain_or_region"},{"id":"T10","span":{"begin":303,"end":308},"obj":"DNA_domain_or_region"},{"id":"T11","span":{"begin":319,"end":346},"obj":"other_name"},{"id":"T12","span":{"begin":363,"end":368},"obj":"DNA_domain_or_region"},{"id":"T13","span":{"begin":390,"end":419},"obj":"DNA_family_or_group"},{"id":"T14","span":{"begin":574,"end":595},"obj":"DNA_domain_or_region"},{"id":"T15","span":{"begin":599,"end":604},"obj":"DNA_domain_or_region"},{"id":"T16","span":{"begin":608,"end":633},"obj":"other_name"},{"id":"T17","span":{"begin":638,"end":664},"obj":"other_name"},{"id":"T18","span":{"begin":668,"end":691},"obj":"cell_line"},{"id":"T19","span":{"begin":708,"end":713},"obj":"DNA_domain_or_region"},{"id":"T20","span":{"begin":731,"end":742},"obj":"DNA_domain_or_region"},{"id":"T21","span":{"begin":744,"end":749},"obj":"DNA_domain_or_region"},{"id":"T22","span":{"begin":755,"end":764},"obj":"DNA_domain_or_region"},{"id":"T23","span":{"begin":790,"end":812},"obj":"DNA_domain_or_region"},{"id":"T24","span":{"begin":825,"end":861},"obj":"cell_line"},{"id":"T25","span":{"begin":870,"end":881},"obj":"DNA_domain_or_region"},{"id":"T26","span":{"begin":910,"end":935},"obj":"cell_line"},{"id":"T27","span":{"begin":960,"end":977},"obj":"DNA_domain_or_region"},{"id":"T28","span":{"begin":1022,"end":1040},"obj":"other_name"},{"id":"T29","span":{"begin":1048,"end":1070},"obj":"DNA_domain_or_region"},{"id":"T30","span":{"begin":1083,"end":1093},"obj":"cell_line"},{"id":"T31","span":{"begin":1178,"end":1200},"obj":"protein_family_or_group"},{"id":"T32","span":{"begin":1209,"end":1240},"obj":"protein_molecule"},{"id":"T33","span":{"begin":1258,"end":1273},"obj":"DNA_domain_or_region"},{"id":"T34","span":{"begin":1293,"end":1335},"obj":"DNA_domain_or_region"},{"id":"T35","span":{"begin":1351,"end":1356},"obj":"DNA_domain_or_region"},{"id":"T36","span":{"begin":1378,"end":1414},"obj":"cell_line"},{"id":"T37","span":{"begin":1426,"end":1436},"obj":"cell_line"},{"id":"T38","span":{"begin":1503,"end":1508},"obj":"DNA_domain_or_region"},{"id":"T39","span":{"begin":1552,"end":1577},"obj":"other_name"},{"id":"T40","span":{"begin":1586,"end":1605},"obj":"other_name"},{"id":"T41","span":{"begin":1695,"end":1728},"obj":"DNA_domain_or_region"},{"id":"T42","span":{"begin":1770,"end":1794},"obj":"protein_family_or_group"}],"text":"Functional roles of in vivo footprinted DNA motifs within an alpha-globin enhancer. Erythroid lineage and developmental stage specificities.\nTranscriptional regulation of the human alpha-like globin genes, embryonic zeta 2 and adult alpha, during erythroid development is mediated by a distal enhancer, HS-40. Previous protein-DNA binding studies have shown that HS-40 consists of multiple nuclear factor binding motifs that are occupied in vivo in an erythroid lineage- and developmental stage-specific manner. We have systematically analyzed the functional roles of these factor binding motifs of HS-40 by site-directed mutagenesis and transient expression assay in erythroid cell cultures. Three of these HS-40 enhancer motifs, 5'NF-E2/AP1, GT II, and GATA-1(c), positively regulate the zeta 2-globin promoter activity in embryonic/fetal erythroid K562 cells and the adult alpha-globin promoter activity in adult erythroid MEL cells. On the other hand, the 3'NF-E2/AP1 motif is able to exert both positive and negative regulatory effects on the zeta 2-globin promoter activity in K562 cells, and this dual function appears to be modulated through differential binding of the ubiquitous AP1 factors and the erythroid-enriched NF-E2 factor. Mutation in the GATA-1(d) motif, which exhibits an adult erythroid-specific genomic footprint, decreases the HS-40 enhancer function in dimethyl sulfoxide-induced MEL cells but not in K562 cells. These studies have defined the regulatory roles of the different HS-40 motifs. The remarkable correlation between genomic footprinting data and the mutagenesis results also suggests that the erythroid lineage- and developmental stage-specific regulation of human alpha-like globin promoters is indeed modulated by stable binding of specific nuclear factors in vivo."}

    Anatomy-MAT

    {"project":"Anatomy-MAT","denotations":[{"id":"T1","span":{"begin":950,"end":954},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"mat_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MAT_0000091"}],"text":"Functional roles of in vivo footprinted DNA motifs within an alpha-globin enhancer. Erythroid lineage and developmental stage specificities.\nTranscriptional regulation of the human alpha-like globin genes, embryonic zeta 2 and adult alpha, during erythroid development is mediated by a distal enhancer, HS-40. Previous protein-DNA binding studies have shown that HS-40 consists of multiple nuclear factor binding motifs that are occupied in vivo in an erythroid lineage- and developmental stage-specific manner. We have systematically analyzed the functional roles of these factor binding motifs of HS-40 by site-directed mutagenesis and transient expression assay in erythroid cell cultures. Three of these HS-40 enhancer motifs, 5'NF-E2/AP1, GT II, and GATA-1(c), positively regulate the zeta 2-globin promoter activity in embryonic/fetal erythroid K562 cells and the adult alpha-globin promoter activity in adult erythroid MEL cells. On the other hand, the 3'NF-E2/AP1 motif is able to exert both positive and negative regulatory effects on the zeta 2-globin promoter activity in K562 cells, and this dual function appears to be modulated through differential binding of the ubiquitous AP1 factors and the erythroid-enriched NF-E2 factor. Mutation in the GATA-1(d) motif, which exhibits an adult erythroid-specific genomic footprint, decreases the HS-40 enhancer function in dimethyl sulfoxide-induced MEL cells but not in K562 cells. These studies have defined the regulatory roles of the different HS-40 motifs. The remarkable correlation between genomic footprinting data and the mutagenesis results also suggests that the erythroid lineage- and developmental stage-specific regulation of human alpha-like globin promoters is indeed modulated by stable binding of specific nuclear factors in vivo."}

    NCBITAXON

    {"project":"NCBITAXON","denotations":[{"id":"T1","span":{"begin":175,"end":180},"obj":"OrganismTaxon"},{"id":"T2","span":{"begin":1695,"end":1700},"obj":"OrganismTaxon"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"9606"},{"id":"A2","pred":"db_id","subj":"T2","obj":"9606"}],"text":"Functional roles of in vivo footprinted DNA motifs within an alpha-globin enhancer. Erythroid lineage and developmental stage specificities.\nTranscriptional regulation of the human alpha-like globin genes, embryonic zeta 2 and adult alpha, during erythroid development is mediated by a distal enhancer, HS-40. Previous protein-DNA binding studies have shown that HS-40 consists of multiple nuclear factor binding motifs that are occupied in vivo in an erythroid lineage- and developmental stage-specific manner. We have systematically analyzed the functional roles of these factor binding motifs of HS-40 by site-directed mutagenesis and transient expression assay in erythroid cell cultures. Three of these HS-40 enhancer motifs, 5'NF-E2/AP1, GT II, and GATA-1(c), positively regulate the zeta 2-globin promoter activity in embryonic/fetal erythroid K562 cells and the adult alpha-globin promoter activity in adult erythroid MEL cells. On the other hand, the 3'NF-E2/AP1 motif is able to exert both positive and negative regulatory effects on the zeta 2-globin promoter activity in K562 cells, and this dual function appears to be modulated through differential binding of the ubiquitous AP1 factors and the erythroid-enriched NF-E2 factor. Mutation in the GATA-1(d) motif, which exhibits an adult erythroid-specific genomic footprint, decreases the HS-40 enhancer function in dimethyl sulfoxide-induced MEL cells but not in K562 cells. These studies have defined the regulatory roles of the different HS-40 motifs. The remarkable correlation between genomic footprinting data and the mutagenesis results also suggests that the erythroid lineage- and developmental stage-specific regulation of human alpha-like globin promoters is indeed modulated by stable binding of specific nuclear factors in vivo."}

    Anatomy-UBERON

    {"project":"Anatomy-UBERON","denotations":[{"id":"T1","span":{"begin":950,"end":954},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/UBERON_0002398"}],"text":"Functional roles of in vivo footprinted DNA motifs within an alpha-globin enhancer. Erythroid lineage and developmental stage specificities.\nTranscriptional regulation of the human alpha-like globin genes, embryonic zeta 2 and adult alpha, during erythroid development is mediated by a distal enhancer, HS-40. Previous protein-DNA binding studies have shown that HS-40 consists of multiple nuclear factor binding motifs that are occupied in vivo in an erythroid lineage- and developmental stage-specific manner. We have systematically analyzed the functional roles of these factor binding motifs of HS-40 by site-directed mutagenesis and transient expression assay in erythroid cell cultures. Three of these HS-40 enhancer motifs, 5'NF-E2/AP1, GT II, and GATA-1(c), positively regulate the zeta 2-globin promoter activity in embryonic/fetal erythroid K562 cells and the adult alpha-globin promoter activity in adult erythroid MEL cells. On the other hand, the 3'NF-E2/AP1 motif is able to exert both positive and negative regulatory effects on the zeta 2-globin promoter activity in K562 cells, and this dual function appears to be modulated through differential binding of the ubiquitous AP1 factors and the erythroid-enriched NF-E2 factor. Mutation in the GATA-1(d) motif, which exhibits an adult erythroid-specific genomic footprint, decreases the HS-40 enhancer function in dimethyl sulfoxide-induced MEL cells but not in K562 cells. These studies have defined the regulatory roles of the different HS-40 motifs. The remarkable correlation between genomic footprinting data and the mutagenesis results also suggests that the erythroid lineage- and developmental stage-specific regulation of human alpha-like globin promoters is indeed modulated by stable binding of specific nuclear factors in vivo."}