Gene Expression in Hematopoietic Cells: The β-Globin Gene

  • Beverly M. Emerson
Part of the Progress in Gene Expression book series (PRGE)


Study of the regulation of gene expression in hematopoietic cells has primarily focused on the globin gene families. These genes are very well characterized in terms of their physical arrangement within the genomes of many different species and in their involvement in hemoglobinopathies (see reviews by Bunn and Forget, 1986; Collins and Weissman, 1984; Nienhuis and Maniatis, 1987; Stamatoyannopoulos and Nienhuis, 1987; Weatherall et al, 1989). The β-globin genes are quite interesting from a transcriptional point of view because their expression is highly erythroid specific and individual members of the multigene family are expressed at defined developmental stages. Transcriptional control is regulated primarily by chromatin structure and the availability of multiple, tissue-specific, trans-acting proteins (see review by Evans et al., 1990). Chromatin structural studies have shown that the entire β-globin gene locus is maintained in an “active” nucleosomal conformation throughout erythroid development although the locus is packaged in an “inactive” conformation in nonexpressing cells. Once the chromosomal locus is activated, individual globin genes are differentially regulated by trans-acting factors operating on specific promoters and enhancers that are associated with each gene.


Globin Gene Erythroid Cell Locus Control Region Gata Site Erythroid Development 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Angel P, Imagawa M, Chiu R, Stein B, Imbra RJ, Rahmsdorf HJ, Jonat C, Herrlich P, Karin M (1987): Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor. Cell 49:729–739.Google Scholar
  2. Antoniou M, deBoer E, Habets G, Grosveld F (1988): The human β-globin gene contains multiple regulatory regions: Identification of one promoter and two downstream enhancers. EMBO J 7:377–384.Google Scholar
  3. Antoniou M, Grosveld F (1990): β-globin dominant control region interacts differently with distal and proximal promoter elements. Genes&Dev 4:1007–1013.Google Scholar
  4. Barberis A, Superti-Furga G, Busslinger M (1987): Mutually exclusive interaction of the CCAAT-binding factor and of a displacement protein with overlapping sequences of a histone gene promoter. Cell 50:347–359.Google Scholar
  5. Behringer RR, Hammer RE, Brinster RL, Palmiter RD, Townes TM (1987): Two 3’ sequences direct adult erythroid-specific expression of human β-globin genes in transgenic mice. Proc Natl Acad Sci USA 84:7056–7060.Google Scholar
  6. Behringer RR, Ryan TM, Palmiter RD, Brinster RL, Townes TM (1990): Human 7- to β-globin gene switching in transgenic mice. Genes & Dev 4:380–389.Google Scholar
  7. Berger SL, Cress WD, Cress A, Triezenberg SJ, Guarente L (1990): Selective inhibition of activated but not basal transcription by the acidic activation domain of VP-16: Evidence for transcriptional adaptors. Cell 61:1199–1208.Google Scholar
  8. Blom van Assendelft M, Hanscombe O, Grosveld F, Greaves DR (1989): The β-globin dominant control region activates homologous and heterologous promoters in a tissue-specific manner. Cell 56:969–977.Google Scholar
  9. Brown JL, Ingram VM (1974): Structural studies on chick embryonic hemoglobins. J Biol Chem 249:3960–3972.Google Scholar
  10. Bruns GA, Ingram VM (1973): The erythroid cells and hemoglobins of the chick embryo. Philos Trans R Soc London (Biol) 266:225–305.Google Scholar
  11. Bunn HF, Forget BG (1986): Hemoglobin: Molecular, Genetic and Clinical Aspects. Philadelphia: WB Saunders.Google Scholar
  12. Cao SX, Gutman PD, Dave HPG, Schechter AN (1989): Identification of a transcriptional silencer in the 5’ flanking region of the human ε-globin gene. Proc Natl Acad Sci USA 86:5306–5309.Google Scholar
  13. Catala F, deBoer E, Habets G, Grosveld F (1989): Nuclear protein factors and erythroid transcription of the human gamma-globin gene. Nucleic Acids Res 17:3811–3827.Google Scholar
  14. Chada K, Magram J, Costantini F (1986): An embryonic pattern of expression of a human fetal globin gene in transgenic mice. Nature (Lond) 319:685–689.Google Scholar
  15. Chapman BS, Tobin AJ (1979): Distribution of developmentally regulated hemoglobins in embryonic erythroid populations. Dev Biol 69:375–387.Google Scholar
  16. Chen R, Ingraham HA, Treacy MN, Albert VR, Wilson L, Rosenfeld MG (1990): Autoregulation of pit-1 gene expression mediated by two cis-active promoter elements. Nature (Lond) 346:583–586.Google Scholar
  17. Chodosh LA, Baldwin AS, Carthew RW, Sharp PA (1988): Human CCAAT-binding proteins have heterologous subunits. Cell 55:11–24.Google Scholar
  18. Choi O-R, Engel JD (1986): A 3’ enhancer is required for temporal and tissue-specific transcriptional activation of the chicken adult β-globin gene. Nature (Lond) 323:731–734.Google Scholar
  19. Choi O-RB, Engel JD (1988): Developmental regulation of β-globin gene switching. Cell 55:17–26.Google Scholar
  20. Collins FS, Cole JL, Lockwood WK, Iannuzzi MC (1987): The deletion in both common types of hereditary persistence of fetal hemoglobin is approximately 105 kb. Blood 70:1797–1803.Google Scholar
  21. Collins FS, Weisman SM (1984): The molecular genetics of human hemoglobin. Prog Nucleic Acid Res Mol Biol 31:315–462.Google Scholar
  22. Collis P, Antoniou M, Grosveld F (1990): Definition of the minimal requirements within the human β-globin gene and the dominant control region for high level expression. EMBO J 9:233–240.Google Scholar
  23. Cowie A, Myers RM (1988): DNA sequences involved in transcriptional regulation of the mouse β-globin promoter in murine erythroleukemia cells. Mol Cell Biol 8:3122–3128.Google Scholar
  24. Curtin PT, Lui D, Lui W, Chang JC, Kan YW (1989): Human β-globin gene expression in transgenic mice is enhanced by a distant DNase-I hypersensitive site. Proc Natl Acad Sci USA 86:7082–7086.Google Scholar
  25. Curtin PT, Pirastu M, Kan YW, Gobert-Jones JA, Stephens AD, Lehmann H (1985): A distant deletion affects β-globin gene function in an atypical γδβ-thalassemia. J Clin Invest 76:1554–1558.Google Scholar
  26. Davidson I, Xiao JH, Rosales R, Staub A, Chambon P (1988): The HeLa cell protein TEF-1 binds specifically and cooperatively to two SV40 enhancer motifs of unrelated sequence. Cell 54:931–942.Google Scholar
  27. deBoer E, Antoniou M, Mignotte V, Wall L, Grosveld F (1988): The human β-globin promoter: Nuclear protein factors and erythroid-specific induction of transcription. EMBO J 7:4203–4212.Google Scholar
  28. Dhar V, Mager D, Iqbal A, Schildkraut CL (1988): The coordinate replication of the human β-globin gene domain reflects its transcriptional activity and nuclease hypersensitivity. Mol Cell Biol 8:4958–4965.Google Scholar
  29. Dhar V, Nandi A, Schildkraut C, Skoultchi AI (1990): Erythroid-specific nuclease hypersensitive sites flanking the human β-globin domain. Mol Cell Biol 10:4324–4333.Google Scholar
  30. Dierks P, van Ooyen A, Cochran MD, Dobkin C, Reiser J, Weissman C (1983): Three regions upstream from the cap site are required for efficient and accurate transcription of the rabbit β-globin gene in mouse 3T6 cells. Cell 32:695–706.Google Scholar
  31. Dillon N, Grosveld F (1991): Human 7-globin genes silenced independently of other genes in the β-globin locus. Nature (Lond) 350:252–254.Google Scholar
  32. Dorfman DM, Wilson DB, Bruns GAP, Orkin SH (1992): Human transcription factor GATA-2. J Biol Chem 267:1279–1285.Google Scholar
  33. Driscoll C, Dobkin CS, Alter BP (1989): γδβ-Thalassemia due to a de novo mutation deleting the 5’ β-globin locus activating region hypersensitive sites. Proc Natl Acad Sci USA 86:7470–7474.Google Scholar
  34. Dynlacht BD, Hoey T, Tjian R (1991): Isolation of coactivators associated with the TATA-binding protein that mediate transcriptional activation. Cell 66:563–576.Google Scholar
  35. Emerson BM, Felsenfeld G (1984): Specific factor conferring nuclease hypersensitivity at the 5′ end of the chicken adult β-globin gene. Proc Natl Acad Sci USA 81:95–99.Google Scholar
  36. Emerson BM, Lewis CD, Felsenfeld G (1985): Interaction of specific nuclear factors with the nuclease-hypersensitive region of the chicken adult β-globin gene: Nature of the binding domain. Cell 41:21–30.Google Scholar
  37. Emerson BM, Nickol JM, Fong TC (1989): Erythroid-specific activation and derepression of the chick β-globin promoter in vitro. Cell 57:1189–1200.Google Scholar
  38. Enver T, Ebens AJ, Forrester WC, Stamatoyannopoulos S (1989): The human β-globin locus activation region alters the developmental fate of a human fetal globin gene in transgenic mice. Proc Natl Acad Sci USA 86:7033–7037.Google Scholar
  39. Enver T, Raich N, Ebens AJ, Papayannopoulou T, Costantini F, Stamatoyannopoulos G (1990): Developmental regulation of human fetal-to-adult globin gene switching in transgenic mice. Nature (Lond) 344:309–313.Google Scholar
  40. Epner E, Forrester WC, Groudine M (1988): Asynchronous DNA replication within the human β-globin gene locus. Proc Natl Acad Sci USA 85:8081–8085.Google Scholar
  41. Epner E, Rifkind R, Marks PA (1981): Replication of a- and β-globin DNA sequencesoccurs during early S phase in murine erythroleukemia cells. Proc Natl Acad Sci USA 78:3058–3062.Google Scholar
  42. Evans T, Felsenfeld G (1989): The erythroid-specific transcription factor eryfl: A new finger protein. Cell 5:877–885.Google Scholar
  43. Evans T, Felsenfeld G (1991): Trans-activation of a globin promoter in non-erythroid cells. Mol Cell Biol 11:843–853.Google Scholar
  44. Evans T, Felsenfeld G, Reitman M (1990): Control of globin gene transcription. Annu Rev Cell Biol 6:95–124.Google Scholar
  45. Evans T, Reitman M, Felsenfeld G (1988): An erythroid-specific DNA-binding factor recognizes a regulatory sequence common to all chicken global genes. Proc Natl Acad Sci USA 85:5976–5980.Google Scholar
  46. Fong TC, Emerson BM: The erythroid-specific protein, cGATA-1, mediates distal enhancer activity through a specialized β-globin TATA box. Genes & Dev (in press).Google Scholar
  47. Forrester WC, Epner E, Driscoll MC, Enver T, Brice M, Papayannopoulou T, Groudine M (1990): A deletion of the human β-globin locus activation region causes a major alteration in chromatin structure and replication across the entire β-globin gene locus. Genes & Dev 4:1637–1649.Google Scholar
  48. Forrester WC, Novak U, Gelinas R, Groudine M (1989): Molecular analysis of the human β-globin locus activation region. Proc Natl Acad Sci USA 86:5439–5443.Google Scholar
  49. Forrester WC, Takegawa S, Papayannopoulou T, Stamatoyannopoulos G, Groudine M (1987): Evidence for a locus activation region: The formation of de-velopmentally stable hypersensitive sites in globin-expressing hybrids. Nucleic Acids Res 15:10159–10177.Google Scholar
  50. Forrester WC, Thompson C, Elder JT, Groudine M (1986): A developmentally stable chromatin structure in the human β-globin gene cluster. Proc Natl Acad Sci USA 83:1359–1363.Google Scholar
  51. Fraser P, Hurst J, Collis P, Grosveld F (1990): DNase I hypersensitive sites 1, 2, and 3 of the human β-globin dominant control region direct position-independent expression. Nucleic Acids Res 18:3503–3508.Google Scholar
  52. Gallarda JL, Foley KP, Yang Z, Engel JD (1989): The β-globin stage selector element factor is erythroid-specific promoter/enhancer binding protein NF-E4. Genes & Dev 3:1845–1859.Google Scholar
  53. Goldman MA, Holmquist GP, Gray MC, Caston LA, Nag A (1984): Replication timing of genes and middle repetitive sequences. Science 224:686–692.Google Scholar
  54. Gottschalk LR, Leiden JM (1990): Identification and functional characterization of the human T-cell receptor β gene transcriptional enhancer: Common nuclear proteins interact with the transcriptional regulatory elements of the T-cell receptor α and β genes. Mol Cell Biol 10:5486–5495.Google Scholar
  55. Grosveld F, van Assendelft GB, Greaves DR, Kollias G (1987): Position-independent, high-level expression of the human β- globin gene in transgenic mice. Cell 51:975–985.Google Scholar
  56. Hannon R, Evans T, Felsenfeld G, Gould H (1991): Structure and promoter activity of the gene for the erythroid transcription factor GATA-1. Proc Natl Acad Sci USA 88:3004–3008.Google Scholar
  57. Hanscombe O, Vidal M, Kaeda J, Luzzatto L, Greaves DR, Grosveld F (1989): High-level, erythroid-specific expression of the human α-globin gene in transgenicmice and the production of human hemoglobin in murine erythrocytes. Genes &Dev 3:1572–1581.Google Scholar
  58. Hanscombe O, Whyatt D, Fraser P, Yannoutsos N, Greaves DR, Dillon N, Grosveld F (1991): Importance of globin gene order for correct developmental expression. Genes & Dev 5:1387–1394.Google Scholar
  59. Hesse JE, Nickol JM, Lieber MR, Felsenfeld G (1986): Regulated gene expression in transfected primary chicken erythrocytes. Proc Natl Acad Sci USA 83:4312–4316.Google Scholar
  60. Higgs DR, Wood WG, Jarman AP, Sharpe J, Lida J, Pretorius IM, Ayyub H (1990): A major positive regulatory region located far upstream of the human α-globin gene locus. Genes & Dev 4:1588–1601.Google Scholar
  61. Ho IC, Vorhees P, Marin N, Oakley BK, Tsai SF, Orkin SH, Leiden JM (1991): Human GATA-3: A lineage-restricted transcription factor that regulates the expression of the T-cell receptor α gene. EMBO J 10:1187–1192.Google Scholar
  62. Ho IC, Yang LH, Morle G, Leiden JM (1989): A T-cell specific transcriptional enhancer element 3′ of Ca in the human T cell receptor a locus. Proc Natl Acad Sci USA 86:6714–6718.Google Scholar
  63. Holmquist GP (1987): Role of replication time in the control of tissue-specific gene expression. Am J Hum Genet 40:151–173.Google Scholar
  64. Horikoshi N, Maguire K, Kralli A, Maldonado E, Weinmann R (1991): Direct interaction between adenovirus El A protein and the TATA box binding transcription factor IID. Proc Natl Acad Sci USA 88:5124–5128.Google Scholar
  65. Jackson PD, Evans T, Nickol JM, Felsenfeld G (1989): Developmental modulation of protein binding to β-globin gene regulatory sites within chicken erythrocyte nuclei. Genes & Dev 3:1860–1873.Google Scholar
  66. Jackson PD, Felsenfeld G (1985): A method for mapping intranuclear protein-DNA interactions and its application to a nuclease hypersensitive site. Proc Natl Acad Sci USA 82:2296–2300.Google Scholar
  67. Joulin V, Bories D, Eleouet JF, Labastie MC, Chretien S, Mattei MG, Romeo PH (1991): A T-cell specific TCR 6 DNA binding protein is a member of the human GATA family. EMBO J 10:1809–1816.Google Scholar
  68. Kadonaga JT, Jones KA, Tjian R (1987): Promoter-specific activation of RNA polymerase II transcription by Spl. Trends Biochem 11:20–23.Google Scholar
  69. Kelleher RJ III, Flanagan PM, Kornberg RD (1990): A novel mediator between activator proteins and the RNA polymerase II transcription apparatus. Cell 61:1209–1215.Google Scholar
  70. Kioussis D, Vanin E, de Lange T, Flavell RA, Grosveld FG (1983): β-globin gene inactivation by DNA translocation in γβ-thalassemia. Nature (Lond) 306:662–666.Google Scholar
  71. Ko LJ, Yamamoto M, Leonard MW, George KM, Ting P, Engel JD (1991): Murine and human T-lymphocyte GATA-3 factors mediate transcription through a cis-regulatory element within the human T-cell receptor 6 gene enhancer. Mol Cell Biol 11:2778–2784.Google Scholar
  72. Kollias G, Hurst J, deBoer E, Grosveld F (1987): The human β-globin gene contains a downstream developmental specific enhancer. Nucleic Acids Res 15:5739–5747.Google Scholar
  73. Kollias G, Wrighton N, Hurst J, Grosveld F (1986): Regulated expression of human Aγ-,β- and hybrid γ/β-globin genes in transgenic mice: Manipulation of the developmental expression patterns. Cell 46:89–94.Google Scholar
  74. Lassar AB, Patterson BM, Weintraub H (1986): Transfection of a DNA locus that mediates the conversion of 10T1/2 fibroblasts to myoblasts. Cell 47:649–656.Google Scholar
  75. Lee W, Mitchell P, Tjian R (1987): Purified transcription factor AP-1 interacts with TRA-inducible enhancer elements. Cell 49:741–752.Google Scholar
  76. Lee WS, Kao CC, Bryant GO, Liu X, Berk AJ (1991): Andenovirus E1A activation domain binds the basic repeat in the TATA box transcription factor. Cell 67:365–376.Google Scholar
  77. Lewis CD, Clark SP, Felsenfeld G, Gould H (1988): An erythrocyte-specific protein that binds to the poly (dG) region of the chicken β-globin gene promoter. Genes & Dev 2:863–873.Google Scholar
  78. Magram J, Niederreither K, Costantini F (1989): β-Globin enhancers target expression of a heterologous gene to erythroid tissues of transgenic mice. Mol Cell Biol 9:4581–4584.Google Scholar
  79. Mantovani R, Malgaretti N, Nicolis S, Giglioni B, Comi P (1988): An erythroid specific nuclear factor binding to the proximal CACCC box of the β-globin gene promoter. Nucleic Acids Res 16:4299–4313.Google Scholar
  80. Mantovani R, Malgaretti N, Giglioni B, Comi P, Cappelini S, Nicolis S, Ottolenghi S (1987): A protein factor binding to an octamer motif in the 7-globin promoter disappears upon induction of differentiation and hemoglobin synthesis in K562 cells. Nucleic Acids Res 15:9349–9364.Google Scholar
  81. Martin DIK, Orkin SH (1990): Transcriptional activation and DNA-binding by the erythroid factor GF-1/NF-El/Eryf 1. Genes & Dev 4:1886–1898.Google Scholar
  82. Martin DIK, Tsai S-F, Orkin SH (1989): Increased gamma-globin expression in a nondeletion HPFH mediated by an erythroid-specific DNA-binding factor. Nature (Lond) 338:435–438.Google Scholar
  83. Martin DIK, Zon LI, Mutter G, Orkin SH (1990): Expression of an erythroid transcription factor in megakaryocyte and mast cell lineages. Nature (Lond) 344:444–447.Google Scholar
  84. McCormick A, Brady H, Theill LE, Karin M (1990): Regulation of the pituitary-specific homeobox gene GHF-1 by cell-autonomous and environmental cues. Nature (Lond) 345:829–832.Google Scholar
  85. McGhee JD, Wood WI, Dolan M, Engel JD, Felsenfeld G (1981): A 200 base pair region at the 5′ end of the chicken adult β-globin gene is accessible to nuclease digestion. Cell 27:45–55.Google Scholar
  86. Meisterernst M, Roy AL, Lieu HM, Roeder RG (1991): Activation of class II gene transcription by regulatory factors is potentiated by a novel activity. Cell 66:981–993.Google Scholar
  87. Mignotte V, Eleouet JF, Raich N, Romeo PH (1989a): Cis- and trans-acting elements involved in the regulation of the erythroid promoter of the human porphobilinogen deaminase gene. Proc Natl Acad Sci USA 86:6548–6552.Google Scholar
  88. Mignotte V, Wall L, deBoer E, Grosveld F, Romeo PH (1989b): Two tissue-specific factors bind the erythroid promoter of the human porphobilinogen deaminase gene. Nucleic Acids Res 17:37–54.Google Scholar
  89. Myers RM, Tilly K, Maniatis T (1986): Fine structure genetic analysis of a β-globin promoter. Science 232:613–618.Google Scholar
  90. Ney PA, Sorrentino BP, McDonagh KT, Nienhuis AW (1990): Tandem AP-1 binding sites within the human β-globin dominant control region function as an inducible enhancer in erythroid cells. Genes & Dev 4:993–1006.Google Scholar
  91. Nickol JM, Felsenfeld G (1988): Bidirectional control of the chicken β- and ε-globin genes by a shared enhancer. Proc Natl Acad Sci USA 85:2548–2552.Google Scholar
  92. Nienhuis AW, Maniatis T (1987): Structure and expression of globin genes in erythroid cells. In: The Molecular Basis of Blood Diseases, Stamoyannopoulos G, Nienhuis AW, Leder P, Majerus PW, eds., pp. 28–65. Philadelphia: WB Saunders.Google Scholar
  93. Nomiyama H, Fromental C, Xiao JH, Chambon P (1987): Cell-specific activity of the constituent elements of the simian virus 40 enhancer. Proc Natl Acad Sci USA 84:7881–7885.Google Scholar
  94. Pevny L, Simon MC, Robertson E, Klein WH, Tsai SF, D’Agati V, Orkin SH, Costantini F (1991): Erythroid differentiation in chimaeric mice blocked by a targeted mutation in the gene for transcription factor GATA-1. Nature (Lond) 349:257–260.Google Scholar
  95. Plumb, MA, Frampton J, Wainwright H, Walker M, Macleod K (1989): GATA AG: A cis-control region binding an erythroid-specific nuclear factor with a role in globin and nonglobin gene expression. Nucleic Acids Res 17:73–91.Google Scholar
  96. Plumb, MA, Lobanenkov VV, Nicolas RH, Wright CA, Zavou S, Goodwin GH (1986): Characterization of chicken erythroid nuclear proteins which bind to the nuclease hypersensitive regions upstream of the β A - and β H -globin genes. Nucleic Acids Res 14:7675–7693.Google Scholar
  97. Ptashne M (1988): How eukaryotic transcriptional activators work. Nature (Lond) 335:683–689.Google Scholar
  98. Pugh BF, Tjian R (1990): Mechanism of transcriptional activation by Spl: Evidence for coactivators. Cell 61:1187–1197.Google Scholar
  99. Raich N, Enver T, Nakamoto B, Josephson B, Papayannopoulou T, Stamatoyannopoulos G (1990): Autonomous developmental control of human embryonic globin gene switching in transgenic mice. Science 250:1147–1149.Google Scholar
  100. Reddy PMS, Shen CKJ (1991): Protein-DNA interactions in vivo of an erythroid-specific, human β-globin locus enhancer. Proc Natl Acad Sci USA 88:8676–8680.Google Scholar
  101. Reitman M, Felsenfeld G (1988): Mutational analysis of the chicken β-globin enhancer reveals two positive-acting domains. Proc Natl Acad Sci USA 85:6264–6271.Google Scholar
  102. Reitman M, Felsenfeld G (1990): Developmental regulation of topoisomerase II sites and DNase-I hypersensitive sites in the chicken β-globin locus. Mol Cell Biol 10:2774–2786.Google Scholar
  103. Redondo JM, Hata S, Brocklehurst C, Krangel MS (1990): A T-cell specific transcriptional enhancer within the human T-cell receptor 6 locus. Science 247:1225–1229.Google Scholar
  104. Romeo PH, Prandini MH, Joulin V, Mignotte V, Prenant M, Vainchenker G, Marguerie G, Uzan G (1990): Megakaryocytc and erythroid lineages share specific transcription factors. Nature (Lond) 344:447–449.Google Scholar
  105. Rosales R, Vigneron M, Macchi M, Davidson I, Xiao J, Chambon P (1987): In vitro binding of cell-specific and ubiquitous nuclear proteins to the octamer motif of the SV40 enhancer and related motifs present in other promoters. EMBO J 6:3015–3025.Google Scholar
  106. Ryan TM, Behringer RR, Townes TM, Palmiter RD, Brinster RL (1989): High-level erythroid expression of human α-globin genes in transgenic mice. Proc Natl Acad Sci USA 86:37–41.Google Scholar
  107. Stamatoyannopoulos G, Nienhuis AW (1987): Hemoglobin switching. In: The Molecular Basis of Blood Diseases, Stamoyannopoulos G, Nienhuis AW, Leder P, Majerus PW, eds., pp. 66–105. Philadelphia: WB Saunders.Google Scholar
  108. Stalder J, Larsen A, Engel JD, Dolan M, Groudine M, Weintraub H (1980): Tissue-specific DNA cleavages in the globin chromatin domain introduced by DNase I. Cell 20:451–460.Google Scholar
  109. Talbot D, Collis P, Antoniou M, Vidal M, Grosveld F, Greaves DR (1989): A dominant control region from the human β-globin locus conferring integration site-independent gene expression. Nature (Lond) 338:352–355.Google Scholar
  110. Talbot D, Grosveld F (1991): The 5’ HS2 of the globin locus control region enhances transcription through the interaction of a multimeric complex binding at two functionally distinct NF-E2 binding sites. EMBO J 10:1391–1398.Google Scholar
  111. Talbot D, Philipsen S, Fraser P, Grosveld F (1990): Detailed analysis of the site 3 region of the human β-globin dominant control region. EMBO J 9:2169–2178.Google Scholar
  112. Taramelli R, Kioussis D, Vanin E, Bartram K, Groffen J, Hurst J, Grosveld F (1986): γβ-thalassemias 1 and 2 are the result of a 100-kb deletion in the human β-globin gene cluster. Nucleic Acids Res 14:7017–7029.Google Scholar
  113. Thayer MJ, Tapscott SJ, Davis RL, Wright WE, Lassar AB, Weintraub H (1989): Positive autoregulation of the myogenic determination gene MyoDl. Cell 58:241–248.Google Scholar
  114. Townes TM, Lingrel JB, Chen HY, Brinster RL, Palmiter RD (1985): Erythroid-specific expression of human β-globin genes in transgenic mice. EMBO J 4:1715–1723.Google Scholar
  115. Trainor CD, Evans T, Felsenfeld G, Boguski MS (1990): Structure and evolution of a human erythroid transcription factor. Nature (Lond) 343:92–96.Google Scholar
  116. Trudel M, Costantini F (1987): A 3’ enhancer contributes to the stage-specific expression of the human β-globin gene. Genes & Dev 1:954–961.Google Scholar
  117. Tsai SF, Martin DI, Zon LI, D’Andrea AD, Wong GG, Orkin SH (1989): Cloning of cDNA for the major DNA-binding protein of the erythroid lineage through expression in mammalian cells. Nature (Lond) 339:446–451.Google Scholar
  118. Tsai SF, Strauss E, Orkin SH (1991): Functional analysis and in vivo footprinting implicate the erythroid transcription factor GATA-1 as a positive regulator of its own promoter. Genes & Dev 5:919–931.Google Scholar
  119. Tuan D, Feingold E, Newman M, Weissman SM, Forget BG (1983): Different 3′ endpoints of deletions causing δβ-thalassemia and hereditary persistence of fetal hemoglobin: Implications for the control of 7-globin gene expression in man. Proc Natl Acad Sci USA 80:6937–6941.Google Scholar
  120. Tuan D, Solomon W, Li Q, London IM (1985): The “β-like globin” gene domain in human erythroid cells. Proc Natl Acad Sci USA 82:6384–6388.Google Scholar
  121. Tuan D, Solomon W, London IM, Lee DP (1989): An erythroid-specific, developmental stage-independent enhancer far upstream of the human “β-like globin” genes. Proc Natl Acad Sci USA 86:2554–2558.Google Scholar
  122. Van der Ploeg LHT, Konings A, Oort M, Roos D, Bernini L, Flavell RA (1980): γβ-Thalassemia studies showing that deletion of the γ- and δ-genes influences β-globin gene expression in man. Nature (Lond) 283:637–642.Google Scholar
  123. Wall L, deBoer E, Grosveld F (1988): The human β-globin gene 3’ enhancer contains multiple binding sites for an erythroid-specific protein. Genes & Dev 2:1089–1100.Google Scholar
  124. Weatherall DJ, Clegg JB, Higgs D, Wood WG (1989): The hemoglobinopathies. In: The Metabolic Basis of Inherited Disease, 6th Ed., Scriver CR, Beaudet AL, Sly WS, Valle D, eds., pp. 2281–2339. New York: McGraw-Hill.Google Scholar
  125. Whitelaw E, Tsai SF, Hogben P, Orkin SH (1990): Regulated expression of globin chains and the erythroid transcription factor (GF-1/NF-El/Eryf 1) during ery-thropoiesis in the developing mouse. Mol Cell Biol 10:6596–6606.Google Scholar
  126. Wilson DB, Dorfman DM, Orkin SH (1990): A non-erythroid GATA-binding protein is required for function of the human preproendothelin-1 promoter in endothelial cells. Mol Cell Biol 10:4854–4862.Google Scholar
  127. Wood WG, Clegg JB, Weatherall DJ (1979): Hereditary persistence of fetal hemoglobin (HPFH) and δβ-thalassemia. Br J Haematol 43:509–520.Google Scholar
  128. Wright S, Rosenthal A, Flavell RA, Grosveld F (1984): DNA sequences required for regulated expression of β-globin genes in murine erythroleukemia cells. Cell 38:265–273.Google Scholar
  129. Xiao JH, Davidson I, Macchi M, Rosales R, Vigneron M (1987): In vitro binding of several cell-specific and ubiquitous nuclear proteins to the GT-1 motif of the SV40 enhancer. Genes & Dev 1:794–807.Google Scholar
  130. Yagi M, Gelinas R, Elder JT, Peretz M, Papayanopoulou T, Stamatoyannopoulos G, Groudine M (1986): Chromatin structure and developmental expression of the human α-globin cluster. Mol Cell Biol 6:1108–1116.Google Scholar
  131. Yamamoto M, Ko LF, Leonard MW, Beug H, Orkin SH, Engel JD (1990): Activity and tissue-specific expression of the transcription factor NF-E1 multigene family. Genes & Dev 4:1650–1662.Google Scholar
  132. Yu C-Y, Chen J, Lin L-I, Tarn M, Shen C-KJ (1990): Cell type-specific protein-DNA interactions in the human ζ-globin upstream promoter region: Displacement of Spl by the erythroid cell-specific factor NF-EI. Mol Cell Biol 10:282–294.Google Scholar
  133. Zon LI, Youssoufian H, Mather C, Lodish HF, Orkin SH (1991a): Activation of the erythropoietin receptor promoter by transcription factor GATA-1. Proc. Natl Acad Sci USA 88:10638–10641.Google Scholar
  134. Zon LI, Mather C, Burgess S, Bolce ME, Harland RM, Orkin SH (1991b): Expression of GATA-binding proteins during embryonic development in Xeno-pus laevis. Proc Natl Acad Sci USA 88:10642–10646.Google Scholar
  135. Zon LI, Gurish MF, Stevens RL, Mather C, Reynolds DS, Austen KF, Orkin SH (1991c): GATA-binding transcription factors in mast cells regulate the promoter of the mast cell carboxypeptidase A gene. J Biol Chem 266:22948–22953.Google Scholar
  136. Zon LI, Tsai SF, Burgess S, Matsudaira P, Bruns GAP, Orkin SH (1990): The major human erythroid DNA-binding protein (GF-1): Primary sequence and localization of the gene to the X chromosome. Proc Natl Acad Sci USA 87:668–672.Google Scholar

Copyright information

© Birkhäuser Boston 1993

Authors and Affiliations

  • Beverly M. Emerson

There are no affiliations available

Personalised recommendations