An insulator element and condensed chromatin region separate the chicken beta-globin locus from an independently regulated erythroid-specific folate receptor gene.
We have identified a folate receptor gene upstream of the chicken beta-globin locus and separated from it by a 16 kbp region of silent chromatin. We find that this receptor is expressed only at a stage of erythroid differentiation (CFU-E) preceding the activation of beta-globin genes, consistent with the role of folate receptors in proliferation. This discovery raises the question of how these two loci are regulated during erythropoiesis. Our data suggest that the folate receptor gene and the beta-globin locus are regulated independently. We show that a 3.3 kbp DNA region upstream of the folate receptor gene is sufficient to induce strong expression of a transgene in CFU-E stage cells. We also find that the region between the beta-globin locus and the folate receptor gene is fully methylated and condensed at this stage of differentiation. Its 3' boundary coincides with the 5' beta-globin insulator. We speculate that the 5' beta-globin boundary element might be important for the proper regulation of two adjacent domains activated at two different stages during differentiation.
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0540, USA.
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Prioleau
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Nony
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Simpson
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Felsenfeld
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002454:Cell Differentiation; D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002642:Chick Embryo; D002645:Chickens / Q000097:blood / Q000235:genetics; D002843:Chromatin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D004706:Endodeoxyribonucleases / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism*; D058973:Folate Receptors, GPI-Anchored; D018628:Gene Dosage; D018507:Gene Expression Regulation, Developmental; D005914:Globins / Q000235:genetics*; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D009928:Organ Specificity; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface; D020218:Response Elements / Q000235:genetics*
D002352:Carrier Proteins; D002843:Chromatin; D058973:Folate Receptors, GPI-Anchored; D020033:Protein Isoforms; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D005914:Globins; D004706:Endodeoxyribonucleases