Home LiteratureArticle Details
PMID: 1875946 Published · ppublish English Journal Article

Characterization of the major regulatory element upstream of the human alpha-globin gene cluster.

Molecular and cellular biology ·Vol. 11 ·No. 9 ·1991-09-00 ·Pages 4679-89

Jarman AP, Wood WG, Sharpe JA, Gourdon G, Ayyub H, Higgs DR

Abstract

The major positive regulatory activity of the human alpha-globin gene complex has been localized to an element associated with a strong erythroid-specific DNase I hypersensitive site (HS -40) located 40 kb upstream of the zeta 2-globin mRNA cap site. Footprint and gel shift analyses of the element have demonstrated the presence of four binding sites for the nuclear factor GATA-1 and two sites corresponding to the AP-1 consensus binding sequence. This region resembles one of the major elements of the beta-globin locus control region in its constitution and characteristics; this together with evidence from expression studies suggests that HS -40 is a primary element controlling alpha-globin gene expression.

Related Genes
MeSH Terms
Base Sequence DNA Deoxyribonuclease I/metabolism Drug Resistance/genetics Electrophoresis, Polyacrylamide Gel Gene Expression Regulation Globins/genetics Humans Molecular Sequence Data Multigene Family Neomycin/pharmacology Regulatory Sequences, Nucleic Acid Restriction Mapping Transformation, Genetic
Chemicals
Globins DNA Deoxyribonuclease I Neomycin
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Jarman A P
MRC Molecular Haematology Unit, John Radcliffe Hospital, Headington, Oxford, United Kingdom.
Wood W G
Sharpe J A
Gourdon G
Ayyub H
Higgs D R
References (53)
53 references, click to expand
  1. A major positive regulatory region located far upstream of the human alpha-globin gene locus.
    Genes Dev. 1990 Sep;4(9):1588-601 PMID: 2253879
  2. The "beta-like-globin" gene domain in human erythroid cells.
    Proc Natl Acad Sci U S A. 1985 Oct;82(19):6384-8 PMID: 3879975
  3. Inactivation of human alpha-globin gene expression by a de novo deletion located upstream of the alpha-globin gene cluster.
    Proc Natl Acad Sci U S A. 1990 Dec;87(23):9431-5 PMID: 1701260
  4. Inducibility of the HS II enhancer depends on binding of an erythroid specific nuclear protein.
    Nucleic Acids Res. 1990 Oct 25;18(20):6011-7 PMID: 2235483
  5. High-level erythroid expression of human alpha-globin genes in transgenic mice.
    Proc Natl Acad Sci U S A. 1989 Jan;86(1):37-41 PMID: 2911581
  6. Evidence for a locus activation region: the formation of developmentally stable hypersensitive sites in globin-expressing hybrids.
    Nucleic Acids Res. 1987 Dec 23;15(24):10159-77 PMID: 3480506
  7. Position-independent, high-level expression of the human beta-globin gene in transgenic mice.
    Cell. 1987 Dec 24;51(6):975-85 PMID: 3690667
  8. Cooperativity of the glucocorticoid receptor and the CACCC-box binding factor.
    Nature. 1988 Mar 3;332(6159):87-90 PMID: 2831456
  9. Developmental regulation of a cloned adult beta-globin gene in transgenic mice.
    Nature. 1985 May 23-29;315(6017):338-40 PMID: 3858676
  10. Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor.
    Cell. 1987 Jun 19;49(6):729-39 PMID: 3034432
  11. Cis- and trans-acting elements involved in the regulation of the erythroid promoter of the human porphobilinogen deaminase gene.
    Proc Natl Acad Sci U S A. 1989 Sep;86(17):6548-52 PMID: 2771941
  12. Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells.
    Cell. 1987 Nov 6;51(3):503-12 PMID: 2822260
  13. The HeLa cell protein TEF-1 binds specifically and cooperatively to two SV40 enhancer motifs of unrelated sequence.
    Cell. 1988 Sep 23;54(7):931-42 PMID: 2843293
  14. Purified transcription factor AP-1 interacts with TPA-inducible enhancer elements.
    Cell. 1987 Jun 19;49(6):741-52 PMID: 3034433
  15. Fos and Jun: the AP-1 connection.
    Cell. 1988 Nov 4;55(3):395-7 PMID: 3141060
  16. O-glycosylation of eukaryotic transcription factors: implications for mechanisms of transcriptional regulation.
    Cell. 1988 Oct 7;55(1):125-33 PMID: 3139301
  17. Nuclease hypersensitive sites in chromatin.
    Annu Rev Biochem. 1988;57:159-97 PMID: 3052270
  18. The human beta-globin gene 3' enhancer contains multiple binding sites for an erythroid-specific protein.
    Genes Dev. 1988 Sep;2(9):1089-100 PMID: 2461328
  19. Cloning of cDNA for the major DNA-binding protein of the erythroid lineage through expression in mammalian cells.
    Nature. 1989 Jun 8;339(6224):446-51 PMID: 2725678
  20. Isolation of cDNA encoding transcription factor Sp1 and functional analysis of the DNA binding domain.
    Cell. 1987 Dec 24;51(6):1079-90 PMID: 3319186
  21. A truncated human chromosome 16 associated with alpha thalassaemia is stabilized by addition of telomeric repeat (TTAGGG)n.
    Nature. 1990 Aug 30;346(6287):868-71 PMID: 1975428
  22. Tandem AP-1-binding sites within the human beta-globin dominant control region function as an inducible enhancer in erythroid cells.
    Genes Dev. 1990 Jun;4(6):993-1006 PMID: 2116990
  23. Human globin locus activation region (LAR): role in temporal control.
    Trends Genet. 1990 Jul;6(7):219-23 PMID: 2202110
  24. Alpha-thalassemia caused by a large (62 kb) deletion upstream of the human alpha globin gene cluster.
    Blood. 1990 Jul 1;76(1):221-7 PMID: 2364173
  25. Definition of the minimal requirements within the human beta-globin gene and the dominant control region for high level expression.
    EMBO J. 1990 Jan;9(1):233-40 PMID: 2295312
  26. Cell type-specific protein-DNA interactions in the human zeta-globin upstream promoter region: displacement of Sp1 by the erythroid cell-specific factor NF-E1.
    Mol Cell Biol. 1990 Jan;10(1):282-94 PMID: 2403638
  27. Detailed analysis of the site 3 region of the human beta-globin dominant control region.
    EMBO J. 1990 Jul;9(7):2169-77 PMID: 2357965
  28. The beta-globin dominant control region: hypersensitive site 2.
    EMBO J. 1990 Jul;9(7):2159-67 PMID: 2357964
  29. Megakaryocytic and erythrocytic lineages share specific transcription factors.
    Nature. 1990 Mar 29;344(6265):447-9 PMID: 2320113
  30. Synergy between the NF-E1 erythroid-specific transcription factor and the CACCC factor in the erythroid-specific promoter of the human porphobilinogen deaminase gene.
    Mol Cell Biol. 1990 Jul;10(7):3838-42 PMID: 2355926
  31. A mutant neomycin phosphotransferase II gene reduces the resistance of transformants to antibiotic selection pressure.
    Proc Natl Acad Sci U S A. 1990 May;87(9):3435-9 PMID: 2159150
  32. Differences in human alpha- and beta-globin gene expression in mouse erythroleukemia cells: the role of intragenic sequences.
    Cell. 1984 Aug;38(1):251-63 PMID: 6205764
  33. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei.
    Nucleic Acids Res. 1983 Mar 11;11(5):1475-89 PMID: 6828386
  34. Sequencing end-labeled DNA with base-specific chemical cleavages.
    Methods Enzymol. 1980;65(1):499-560 PMID: 6246368
  35. Isolation of transforming DNA: cloning the hamster aprt gene.
    Cell. 1980 Dec;22(3):817-23 PMID: 7460013
  36. Chromosomal subunits in active genes have an altered conformation.
    Science. 1976 Sep 3;193(4256):848-56 PMID: 948749
  37. GATAAG; a cis-control region binding an erythroid-specific nuclear factor with a role in globin and non-globin gene expression.
    Nucleic Acids Res. 1989 Jan 11;17(1):73-92 PMID: 2911489
  38. Two tissue-specific factors bind the erythroid promoter of the human porphobilinogen deaminase gene.
    Nucleic Acids Res. 1989 Jan 11;17(1):37-54 PMID: 2911469
  39. Identification and characterization of a chicken alpha-globin enhancer.
    Mol Cell Biol. 1989 Mar;9(3):893-901 PMID: 2725505
  40. The human beta-globin promoter; nuclear protein factors and erythroid specific induction of transcription.
    EMBO J. 1988 Dec 20;7(13):4203-12 PMID: 3243278
  41. The beta-globin dominant control region activates homologous and heterologous promoters in a tissue-specific manner.
    Cell. 1989 Mar 24;56(6):969-77 PMID: 2924354
  42. A dominant control region from the human beta-globin locus conferring integration site-independent gene expression.
    Nature. 1989 Mar 23;338(6213):352-5 PMID: 2922063
  43. A single erythroid-specific DNase I super-hypersensitive site activates high levels of human beta-globin gene expression in transgenic mice.
    Genes Dev. 1989 Mar;3(3):314-23 PMID: 2721958
  44. An erythroid-specific, developmental-stage-independent enhancer far upstream of the human "beta-like globin" genes.
    Proc Natl Acad Sci U S A. 1989 Apr;86(8):2554-8 PMID: 2704733
  45. Molecular analysis of the human beta-globin locus activation region.
    Proc Natl Acad Sci U S A. 1989 Jul;86(14):5439-43 PMID: 2748594
  46. Human beta-globin gene expression in transgenic mice is enhanced by a distant DNase I hypersensitive site.
    Proc Natl Acad Sci U S A. 1989 Sep;86(18):7082-6 PMID: 2780563
  47. Synthesis of functional human hemoglobin in transgenic mice.
    Science. 1989 Sep 1;245(4921):971-3 PMID: 2772649
  48. Mutational analysis of the chicken beta-globin enhancer reveals two positive-acting domains.
    Proc Natl Acad Sci U S A. 1988 Sep;85(17):6267-71 PMID: 3166139
  49. An erythrocyte-specific DNA-binding factor recognizes a regulatory sequence common to all chicken globin genes.
    Proc Natl Acad Sci U S A. 1988 Aug;85(16):5976-80 PMID: 3413070
  50. High-level, erythroid-specific expression of the human alpha-globin gene in transgenic mice and the production of human hemoglobin in murine erythrocytes.
    Genes Dev. 1989 Oct;3(10):1572-81 PMID: 2612906
  51. Developmental modulation of protein binding to beta-globin gene regulatory sites within chicken erythrocyte nuclei.
    Genes Dev. 1989 Dec;3(12A):1860-73 PMID: 2620826
  52. Regulated expression of human A gamma-, beta-, and hybrid gamma beta-globin genes in transgenic mice: manipulation of the developmental expression patterns.
    Cell. 1986 Jul 4;46(1):89-94 PMID: 3719696
  53. Conservation of the primary structure, organization, and function of the human and mouse beta-globin locus-activating regions.
    Proc Natl Acad Sci U S A. 1990 Oct;87(19):7693-7 PMID: 2217202
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
Published
1991-09-00
Pages
4679-89
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC361359
Subset
IM
Databases
GENBANK
M64827, S43604, S43609, S43613, S43614, S43616, S43620, S49742, S49899, X57834
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]