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PMID: 14749362 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

SCL assembles a multifactorial complex that determines glycophorin A expression.

Molecular and cellular biology ·Vol. 24 ·No. 4 ·2004-02-00 ·Pages 1439-52

Lahlil R, Lécuyer E, Herblot S, Hoang T

Abstract

SCL/TAL1 is a hematopoietic-specific transcription factor of the basic helix-loop-helix (bHLH) family that is essential for erythropoiesis. Here we identify the erythroid cell-specific glycophorin A gene (GPA) as a target of SCL in primary hematopoietic cells and show that SCL occupies the GPA locus in vivo. GPA promoter activation is dependent on the assembly of a multifactorial complex containing SCL as well as ubiquitous (E47, Sp1, and Ldb1) and tissue-specific (LMO2 and GATA-1) transcription factors. In addition, our observations suggest functional specialization within this complex, as SCL provides its HLH protein interaction motif, GATA-1 exerts a DNA-tethering function through its binding to a critical GATA element in the GPA promoter, and E47 requires its N-terminal moiety (most likely entailing a transactivation function). Finally, endogenous GPA expression is disrupted in hematopoietic cells through the dominant-inhibitory effect of a truncated form of E47 (E47-bHLH) on E-protein activity or of FOG (Friend of GATA) on GATA activity or when LMO2 or Ldb-1 protein levels are decreased. Together, these observations reveal the functional complementarities of transcription factors within the SCL complex and the essential role of SCL as a nucleation factor within a higher-order complex required to activate gene GPA expression.

MeSH Terms
Adaptor Proteins, Signal Transducing Animals Base Sequence Basic Helix-Loop-Helix Transcription Factors Binding Sites Cell Line DNA-Binding Proteins/chemistry,metabolism Electrophoretic Mobility Shift Assay Erythroid-Specific DNA-Binding Factors GATA1 Transcription Factor Gene Expression Regulation Glycophorins/genetics Hematopoietic Stem Cells/metabolism LIM Domain Proteins Macromolecular Substances Metalloproteins/metabolism Mice Molecular Sequence Data Promoter Regions, Genetic/genetics Protein Binding Protein Structure, Tertiary Proto-Oncogene Proteins/chemistry,metabolism Response Elements Reverse Transcriptase Polymerase Chain Reaction Sp1 Transcription Factor/metabolism T-Cell Acute Lymphocytic Leukemia Protein 1 TCF Transcription Factors Transcription Factor 7-Like 1 Protein Transcription Factors/chemistry,metabolism
Chemicals
Adaptor Proteins, Signal Transducing Basic Helix-Loop-Helix Transcription Factors DNA-Binding Proteins Erythroid-Specific DNA-Binding Factors GATA1 Transcription Factor Gata1 protein, mouse Glycophorins LDB1 protein, human LIM Domain Proteins Ldb1 protein, mouse Lmo2 protein, mouse Macromolecular Substances Metalloproteins Proto-Oncogene Proteins Sp1 Transcription Factor T-Cell Acute Lymphocytic Leukemia Protein 1 TCF Transcription Factors TCF7L1 protein, human Tal1 protein, mouse Tcf7l1 protein, mouse Transcription Factor 7-Like 1 Protein Transcription Factors
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Lahlil Rachid
Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada.
Lécuyer Eric
Herblot Sabine
Hoang Trang
References (71)
71 references, click to expand
  1. The oncogenic T cell LIM-protein Lmo2 forms part of a DNA-binding complex specifically in immature T cells.
    EMBO J. 1998 Aug 17;17(16):4594-605 PMID: 9707419
  2. Characterization of hematopoietic progenitor cells that express the transcription factor SCL, using a lacZ "knock-in" strategy.
    Proc Natl Acad Sci U S A. 1998 Sep 29;95(20):11897-902 PMID: 9751762
  3. A transcription factor party during blood cell differentiation.
    Curr Opin Genet Dev. 1998 Oct;8(5):545-51 PMID: 9794826
  4. TAL1 and LIM-only proteins synergistically induce retinaldehyde dehydrogenase 2 expression in T-cell acute lymphoblastic leukemia by acting as cofactors for GATA3.
    Mol Cell Biol. 1998 Dec;18(12):6939-50 PMID: 9819382
  5. The relative expression amounts of apterous and its co-factor dLdb/Chip are critical for dorso-ventral compartmentalization in the Drosophila wing.
    EMBO J. 1998 Dec 1;17(23):6846-53 PMID: 9843490
  6. The hematopoietic transcription factor SCL binds the p44 subunit of TFIIH.
    J Biol Chem. 1999 Jan 15;274(3):1388-93 PMID: 9880511
  7. Use of altered specificity mutants to probe a specific protein-protein interaction in differentiation: the GATA-1:FOG complex.
    Mol Cell. 1999 Feb;3(2):219-28 PMID: 10078204
  8. Expression of TAL-1 proteins in human tissues.
    Blood. 1995 Feb 1;85(3):675-84 PMID: 7833471
  9. Functional synergy and physical interactions of the erythroid transcription factor GATA-1 with the Krüppel family proteins Sp1 and EKLF.
    Mol Cell Biol. 1995 May;15(5):2437-47 PMID: 7739528
  10. Self-association of the erythroid transcription factor GATA-1 mediated by its zinc finger domains.
    Mol Cell Biol. 1995 May;15(5):2448-56 PMID: 7739529
  11. Absence of yolk sac hematopoiesis from mice with a targeted disruption of the scl gene.
    Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):7075-9 PMID: 7624372
  12. Association of erythroid transcription factors: complexes involving the LIM protein RBTN2 and the zinc-finger protein GATA1.
    Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9585-9 PMID: 7568177
  13. Analysis of gene expression in a complex differentiation hierarchy by global amplification of cDNA from single cells.
    Curr Biol. 1995 Aug 1;5(8):909-22 PMID: 7583149
  14. Opposing effects of the basic helix-loop-helix transcription factor SCL on erythroid and monocytic differentiation.
    Blood. 1996 Jan 1;87(1):102-11 PMID: 8547631
  15. The E-box of the human glycophorin B promoter is involved in the erythroid-specific expression of the GPB gene.
    Biochem Biophys Res Commun. 1999 Nov;265(1):170-6 PMID: 10548509
  16. SCL expression in the mouse embryo detected with a targeted lacZ reporter gene demonstrates its localization to hematopoietic, vascular, and neural tissues.
    Blood. 1999 Dec 1;94(11):3754-63 PMID: 10572089
  17. The GATA-E box-GATA motif in the EKLF promoter is required for in vivo expression.
    Blood. 2000 Mar 1;95(5):1652-5 PMID: 10688820
  18. Chip interacts with diverse homeodomain proteins and potentiates bicoid activity in vivo.
    Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2686-91 PMID: 10688916
  19. The level of DLDB/CHIP controls the activity of the LIM homeodomain protein apterous: evidence for a functional tetramer complex in vivo.
    EMBO J. 2000 Jun 1;19(11):2602-14 PMID: 10835358
  20. Specific protein-protein interaction between basic helix-loop-helix transcription factors and homeoproteins of the Pitx family.
    Mol Cell Biol. 2000 Jul;20(13):4826-37 PMID: 10848608
  21. Interactions between chip and the achaete/scute-daughterless heterodimers are required for pannier-driven proneural patterning.
    Mol Cell. 2000 Oct;6(4):781-90 PMID: 11090617
  22. SCL and LMO1 alter thymocyte differentiation: inhibition of E2A-HEB function and pre-T alpha chain expression.
    Nat Immunol. 2000 Aug;1(2):138-44 PMID: 11248806
  23. Glycophorin A dimerization and band 3 interaction during erythroid membrane biogenesis: in vivo studies in human glycophorin A transgenic mice.
    Blood. 2001 May 1;97(9):2872-8 PMID: 11313283
  24. Primitive erythropoiesis in the Xenopus embryo: the synergistic role of LMO-2, SCL and GATA-binding proteins.
    Development. 2001 Jun;128(12):2301-8 PMID: 11493549
  25. Selective rescue of early haematopoietic progenitors in Scl(-/-) mice by expressing Scl under the control of a stem cell enhancer.
    Development. 2001 Dec;128(23):4815-27 PMID: 11731461
  26. Absence of CD47 in protein 4.2-deficient hereditary spherocytosis in man: an interaction between the Rh complex and the band 3 complex.
    Blood. 2002 Sep 1;100(5):1878-85 PMID: 12176912
  27. The SCL complex regulates c-kit expression in hematopoietic cells through functional interaction with Sp1.
    Blood. 2002 Oct 1;100(7):2430-40 PMID: 12239153
  28. Functional ablation of the mouse Ldb1 gene results in severe patterning defects during gastrulation.
    Development. 2003 Feb;130(3):495-505 PMID: 12490556
  29. Haematopoietic stem cells retain long-term repopulating activity and multipotency in the absence of stem-cell leukaemia SCL/tal-1 gene.
    Nature. 2003 Jan 30;421(6922):547-51 PMID: 12540851
  30. The critical regulator of embryonic hematopoiesis, SCL, is vital in the adult for megakaryopoiesis, erythropoiesis, and lineage choice in CFU-S12.
    Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):992-7 PMID: 12552125
  31. Regulation of pT alpha gene expression by a dosage of E2A, HEB, and SCL.
    J Biol Chem. 2003 Apr 11;278(15):12680-7 PMID: 12566462
  32. Identification of a TAL1 target gene reveals a positive role for the LIM domain-binding protein Ldb1 in erythroid gene expression and differentiation.
    Mol Cell Biol. 2003 Nov;23(21):7585-99 PMID: 14560005
  33. Red blood cell glycophorins.
    Blood. 1992 Oct 15;80(8):1869-79 PMID: 1391951
  34. The SCL gene product: a positive regulator of erythroid differentiation.
    EMBO J. 1992 Nov;11(11):4073-81 PMID: 1396592
  35. Erythroid-specific activity of the glycophorin B promoter requires GATA-1 mediated displacement of a repressor.
    EMBO J. 1992 Nov;11(11):4095-102 PMID: 1396593
  36. Specificity of single LIM motifs in targeting and LIM/LIM interactions in situ.
    Genes Dev. 1996 Feb 1;10(3):289-300 PMID: 8595880
  37. Reduced invasion and growth of Plasmodium falciparum into elliptocytic red blood cells with a combined deficiency of protein 4.1, glycophorin C, and p55.
    Blood. 1996 Apr 15;87(8):3462-9 PMID: 8605365
  38. The SCL gene: from case report to critical hematopoietic regulator.
    Blood. 1999 May 1;93(9):2760-70 PMID: 10216069
  39. Transcriptional cofactors of the FOG family interact with GATA proteins by means of multiple zinc fingers.
    EMBO J. 1999 May 17;18(10):2812-22 PMID: 10329627
  40. Different sequence requirements for expression in erythroid and megakaryocytic cells within a regulatory element upstream of the GATA-1 gene.
    Development. 1999 Jun;126(12):2799-811 PMID: 10331989
  41. A conserved motif present in a class of helix-loop-helix proteins activates transcription by direct recruitment of the SAGA complex.
    Mol Cell. 1999 Jul;4(1):63-73 PMID: 10445028
  42. Chip and apterous physically interact to form a functional complex during Drosophila development.
    Mol Cell. 1999 Aug;4(2):259-65 PMID: 10488341
  43. Regulation of LIM homeodomain activity in vivo: a tetramer of dLDB and apterous confers activity and capacity for regulation by dLMO.
    Mol Cell. 1999 Aug;4(2):267-73 PMID: 10488342
  44. Specification of hematopoietic and vascular development by the bHLH transcription factor SCL without direct DNA binding.
    Development. 1999 Oct;126(20):4603-15 PMID: 10498694
  45. Identification of a precursor genomic segment that provided a sequence unique to glycophorin B and E genes.
    Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7220-4 PMID: 8346238
  46. Preferred sequences for DNA recognition by the TAL1 helix-loop-helix proteins.
    Mol Cell Biol. 1994 Feb;14(2):1256-65 PMID: 8289805
  47. The SCL/TAL-1 gene is expressed in progenitors of both the hematopoietic and vascular systems during embryogenesis.
    Blood. 1994 Mar 1;83(5):1200-8 PMID: 8118024
  48. Altered band 3 structure and function in glycophorin A- and B-deficient (MkMk) red blood cells.
    Blood. 1994 Aug 1;84(3):916-22 PMID: 8043873
  49. Novel insights into erythroid development revealed through in vitro differentiation of GATA-1 embryonic stem cells.
    Genes Dev. 1994 May 15;8(10):1184-97 PMID: 7926723
  50. The LIM/double zinc-finger motif functions as a protein dimerization domain.
    Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10655-9 PMID: 7938009
  51. Specific in vivo association between the bHLH and LIM proteins implicated in human T cell leukemia.
    EMBO J. 1994 Oct 17;13(20):4831-9 PMID: 7957052
  52. Post-transcriptional regulation of the cell surface expression of glycophorins A, B, and E.
    J Biol Chem. 1994 Dec 30;269(52):32752-8 PMID: 7806496
  53. Absence of blood formation in mice lacking the T-cell leukaemia oncoprotein tal-1/SCL.
    Nature. 1995 Feb 2;373(6513):432-4 PMID: 7830794
  54. The T cell leukemia oncoprotein SCL/tal-1 is essential for development of all hematopoietic lineages.
    Cell. 1996 Jul 12;86(1):47-57 PMID: 8689686
  55. The scl gene product is required for the generation of all hematopoietic lineages in the adult mouse.
    EMBO J. 1996 Aug 15;15(16):4123-9 PMID: 8861941
  56. A stable human-derived packaging cell line for production of high titer retrovirus/vesicular stomatitis virus G pseudotypes.
    Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11400-6 PMID: 8876147
  57. Multilineage gene expression precedes commitment in the hemopoietic system.
    Genes Dev. 1997 Mar 15;11(6):774-85 PMID: 9087431
  58. Transcription factor GATA-2 is required for proliferation/survival of early hematopoietic cells and mast cell formation, but not for erythroid and myeloid terminal differentiation.
    Blood. 1997 May 15;89(10):3636-43 PMID: 9160668
  59. An scl gene product lacking the transactivation domain induces bony abnormalities and cooperates with LMO1 to generate T-cell malignancies in transgenic mice.
    EMBO J. 1997 May 1;16(9):2408-19 PMID: 9171354
  60. The LIM-only protein Lmo2 is a bridging molecule assembling an erythroid, DNA-binding complex which includes the TAL1, E47, GATA-1 and Ldb1/NLI proteins.
    EMBO J. 1997 Jun 2;16(11):3145-57 PMID: 9214632
  61. Transcription factors, normal myeloid development, and leukemia.
    Blood. 1997 Jul 15;90(2):489-519 PMID: 9226149
  62. FOG, a multitype zinc finger protein, acts as a cofactor for transcription factor GATA-1 in erythroid and megakaryocytic differentiation.
    Cell. 1997 Jul 11;90(1):109-19 PMID: 9230307
  63. Chip, a widely expressed chromosomal protein required for segmentation and activity of a remote wing margin enhancer in Drosophila.
    Genes Dev. 1997 Oct 15;11(20):2729-40 PMID: 9334334
  64. The LIM-domain binding protein Ldb1 and its partner LMO2 act as negative regulators of erythroid differentiation.
    Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13707-12 PMID: 9391090
  65. Enforced TAL-1 expression stimulates primitive, erythroid and megakaryocytic progenitors but blocks the granulopoietic differentiation program.
    Cancer Res. 1998 Feb 1;58(3):562-9 PMID: 9458106
  66. Complete deficiency of glycophorin A in red blood cells from mice with targeted inactivation of the band 3 (AE1) gene.
    Blood. 1998 Mar 15;91(6):2146-51 PMID: 9490702
  67. Failure of megakaryopoiesis and arrested erythropoiesis in mice lacking the GATA-1 transcriptional cofactor FOG.
    Genes Dev. 1998 Apr 15;12(8):1176-88 PMID: 9553047
  68. Enhanced megakaryocyte and erythroid development from normal human CD34(+) cells: consequence of enforced expression of SCL.
    Blood. 1998 May 15;91(10):3756-65 PMID: 9573012
  69. SCL specifies hematopoietic mesoderm in Xenopus embryos.
    Development. 1998 Jul;125(14):2611-20 PMID: 9636076
  70. The SCL gene specifies haemangioblast development from early mesoderm.
    EMBO J. 1998 Jul 15;17(14):4029-45 PMID: 9670018
  71. Transcription factor SCL is required for c-kit expression and c-Kit function in hemopoietic cells.
    J Exp Med. 1998 Aug 3;188(3):439-50 PMID: 9687522
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.24.4.1439-1452.2004
Published
2004-02-00
Pages
1439-52
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC344179
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.24.4.1439-1452.2004 PMC Full Text View journal details
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