Home LiteratureArticle Details
PMID: 8622684 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A DNA-bending protein interacts with an essential upstream regulatory element of the human embryonic beta-like globin gene.

Molecular and cellular biology ·Vol. 16 ·No. 3 ·1996-03-00 ·Pages 829-38

Dyer MA, Naidoo R, Hayes RJ, Larson CJ, Verdine GL, Baron MH

Abstract

The mammalian beta-like globin gene family has served as an important model system for analysis of tissue- and developmental state-specific gene regulation. Although the activities of a number of regulatory proteins have been implicated in the erythroid cell-specific transcription of globin genes, the mechanisms that restrict their expression to discrete stages of development are less well understood. We have previously identified a novel regulatory element (PRE II) upstream from the human embryonic beta-like globin gene (epsilon) that synergizes with other sequences to confer tissue- and stage-specific expression on a minimal epsilon-globin gene promoter in cultured embryonic erythroid cells. Binding of an erythroid nuclear protein (PRE II-binding factor [PRE-IIBF]) to the PRE II control element is required for promoter activation. Here we report on some of the biochemical properties of PREIIBF, including the characterization of its specificity and affinity for DNA. The embryonic and adult forms of PREIIBF recognize their cognate sequences with identical specificities, supporting our earlier conclusion that they are very similar proteins. PREIIBF binds DNA as a single polypeptide with an Mr of approximately 80,000 to 85,000 and introduces a bend into the target DNA molecule. These results suggest a mechanism by which PREIIBF may contribute to the regulation of the embryonic beta-like globin gene within the context of a complex locus.

MeSH Terms
Base Sequence Cell Line DNA-Binding Proteins/metabolism Embryo, Mammalian/metabolism Erythrocytes/metabolism Female Gene Expression Regulation, Developmental Globins/genetics,metabolism Humans Molecular Sequence Data Pregnancy Regulatory Sequences, Nucleic Acid/genetics
Chemicals
DNA-Binding Proteins Globins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Dyer M A
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Naidoo R
Hayes R J
Larson C J
Verdine G L
Baron M H
References (64)
64 references, click to expand
  1. HMG domain proteins: architectural elements in the assembly of nucleoprotein structures.
    Trends Genet. 1994 Mar;10(3):94-100 PMID: 8178371
  2. Structural basis for DNA bending by the architectural transcription factor LEF-1.
    Nature. 1995 Aug 31;376(6543):791-5 PMID: 7651541
  3. The oncogenic cysteine-rich LIM domain protein rbtn2 is essential for erythroid development.
    Cell. 1994 Jul 15;78(1):45-57 PMID: 8033210
  4. Bending of DNA by gene-regulatory proteins: construction and use of a DNA bending vector.
    Gene. 1989 Dec 21;85(1):15-23 PMID: 2533576
  5. A new model for the bending of DNAs containing the oligo(dA) tracts based on NMR observations.
    Nucleic Acids Res. 1990 Feb 11;18(3):613-8 PMID: 2308847
  6. DNA binding properties of the purified Antennapedia homeodomain.
    Proc Natl Acad Sci U S A. 1990 Jun;87(11):4093-7 PMID: 1971945
  7. Molecular characterization of the GCN4-DNA complex.
    Proc Natl Acad Sci U S A. 1990 Aug;87(16):6034-8 PMID: 2201019
  8. Ubiquitous transcription factor OTF-1 mediates induction of the MMTV promoter through synergistic interaction with hormone receptors.
    Cell. 1991 Feb 8;64(3):565-72 PMID: 1846780
  9. Regulated expression of human alpha- and beta-globin genes in transient heterokaryons.
    Mol Cell Biol. 1991 Mar;11(3):1239-47 PMID: 1705003
  10. HMG1-related DNA-binding protein isolated with V-(D)-J recombination signal probes.
    Mol Cell Biol. 1991 Sep;11(9):4528-36 PMID: 1678855
  11. POU proteins bend DNA via the POU-specific domain.
    EMBO J. 1991 Oct;10(10):3007-14 PMID: 1915275
  12. DNA bending by Fos and Jun: the flexible hinge model.
    Science. 1991 Nov 22;254(5035):1210-4 PMID: 1957173
  13. Purification of sequence-specific binding proteins by DNA affinity chromatography.
    Methods Enzymol. 1991;208:10-23 PMID: 1779831
  14. DNA bending in protein-DNA complexes.
    Methods Enzymol. 1991;208:118-46 PMID: 1779833
  15. Demonstration of a human epsilon-globin gene silencer with studies in transgenic mice.
    Blood. 1992 Feb 15;79(4):861-4 PMID: 1737096
  16. Binding of erythroid and non-erythroid nuclear proteins to the silencer of the human epsilon-globin-encoding gene.
    Gene. 1992 Jan 15;110(2):197-203 PMID: 1537556
  17. Specific binding of chromosomal protein HMG1 to DNA damaged by the anticancer drug cisplatin.
    Science. 1992 Apr 10;256(5054):234-7 PMID: 1566071
  18. The epsilon-globin gene silencer. Characterization by in vitro transcription.
    J Biol Chem. 1992 Jun 5;267(16):11532-8 PMID: 1597481
  19. A high-capacity column for affinity purification of sequence-specific DNA-binding proteins.
    Nucleic Acids Res. 1992 Jul 11;20(13):3525 PMID: 1630934
  20. Myc/Max and other helix-loop-helix/leucine zipper proteins bend DNA toward the minor groove.
    Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11779-83 PMID: 1465398
  21. Each hypersensitive site of the human beta-globin locus control region confers a different developmental pattern of expression on the globin genes.
    Genes Dev. 1993 Jan;7(1):106-13 PMID: 8422981
  22. Erythroid transcription factor NF-E2 is a haematopoietic-specific basic-leucine zipper protein.
    Nature. 1993 Apr 22;362(6422):722-8 PMID: 8469283
  23. A novel, erythroid cell-specific murine transcription factor that binds to the CACCC element and is related to the Krüppel family of nuclear proteins.
    Mol Cell Biol. 1993 May;13(5):2776-86 PMID: 7682653
  24. Transcriptional regulation of multigene loci: multilevel control.
    Trends Genet. 1993 Apr;9(4):134-7 PMID: 8516848
  25. Functional and physical associations between NF-kappa B and C/EBP family members: a Rel domain-bZIP interaction.
    Mol Cell Biol. 1993 Jul;13(7):3964-74 PMID: 8321203
  26. Identification and characterization of a beta-globin promoter-binding factor from murine erythroleukemia cells.
    Mol Cell Biol. 1993 Jul;13(7):4311-22 PMID: 8321233
  27. Selective DNA bending by a variety of bZIP proteins.
    Mol Cell Biol. 1993 Sep;13(9):5479-89 PMID: 8355695
  28. Purification of the major histocompatibility complex class I transcription factor H2TF1. The full-length product of the nfkb2 gene.
    J Biol Chem. 1993 Sep 5;268(25):18882-90 PMID: 8360178
  29. Mechanisms of transcriptional synergism between distinct virus-inducible enhancer elements.
    Cell. 1993 Sep 10;74(5):887-98 PMID: 8374955
  30. Isolation of the cyclosporin-sensitive T cell transcription factor NFATp.
    Science. 1993 Oct 29;262(5134):750-4 PMID: 8235597
  31. Developmental regulation of human beta-globin gene transcription: a switch of loyalties?
    Trends Genet. 1993 Sep;9(9):304-9 PMID: 8236459
  32. Developmental regulation of the human embryonic beta-like globin gene is mediated by synergistic interactions among multiple tissue- and stage-specific elements.
    Mol Cell Biol. 1993 Dec;13(12):7457-68 PMID: 8246963
  33. DNA bending and orientation-dependent function of YY1 in the c-fos promoter.
    Genes Dev. 1993 Dec;7(12B):2497-509 PMID: 8276234
  34. Transcriptional activation: a complex puzzle with few easy pieces.
    Cell. 1994 Apr 8;77(1):5-8 PMID: 8156597
  35. Positive regulators of the lineage-specific transcription factor GATA-1 in differentiating erythroid cells.
    Mol Cell Biol. 1994 May;14(5):3108-14 PMID: 8164666
  36. Architectural transcription factors.
    Science. 1994 May 20;264(5162):1100-1 PMID: 8178167
  37. The enhancer-blocking suppressor of Hairy-wing zinc finger protein of Drosophila melanogaster alters DNA structure.
    Mol Cell Biol. 1994 Sep;14(9):5645-52 PMID: 8065301
  38. The C/EBP family of proteins distorts DNA upon binding but does not introduce a large directed bend.
    J Biol Chem. 1994 Sep 23;269(38):23553-62 PMID: 8089123
  39. Cloning and characterization of seven human forkhead proteins: binding site specificity and DNA bending.
    EMBO J. 1994 Oct 17;13(20):5002-12 PMID: 7957066
  40. Crystal structure of the heterodimeric bZIP transcription factor c-Fos-c-Jun bound to DNA.
    Nature. 1995 Jan 19;373(6511):257-61 PMID: 7816143
  41. Upstream regulatory region of the human embryonic beta-like globin gene, epsilon.
    DNA Seq. 1994;4(6):409-12 PMID: 7841465
  42. Homodimer of p50 (NF kappa B1) does not introduce a substantial directed bend into DNA according to three different experimental assays.
    Nucleic Acids Res. 1995 Feb 11;23(3):427-33 PMID: 7885838
  43. 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
  44. Defective haematopoiesis in fetal liver resulting from inactivation of the EKLF gene.
    Nature. 1995 May 25;375(6529):316-8 PMID: 7753194
  45. Lac repressor-operator interaction. I. Equilibrium studies.
    J Mol Biol. 1970 Feb 28;48(1):67-83 PMID: 4915295
  46. beta-globin transcript found in induced murine erythroleukemia cells is homologous to the beta h0 and beta h1 genes.
    Proc Natl Acad Sci U S A. 1982 May;79(9):2753-7 PMID: 6953428
  47. The regulated expression of beta-globin genes introduced into mouse erythroleukemia cells.
    Cell. 1983 Feb;32(2):483-93 PMID: 6572107
  48. 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
  49. K562 human leukemia cell passages differ in embryonic globin gene expression.
    Leuk Res. 1984;8(1):45-54 PMID: 6199625
  50. The locus of sequence-directed and protein-induced DNA bending.
    Nature. 1984 Apr 5-11;308(5959):509-13 PMID: 6323997
  51. Rapid reprogramming of globin gene expression in transient heterokaryons.
    Cell. 1986 Aug 15;46(4):591-602 PMID: 3731277
  52. Position-independent, high-level expression of the human beta-globin gene in transgenic mice.
    Cell. 1987 Dec 24;51(6):975-85 PMID: 3690667
  53. Plasmid permutation vectors to monitor DNA bending.
    Nucleic Acids Res. 1987 Dec 10;15(23):10060 PMID: 3697072
  54. Empirical estimation of protein-induced DNA bending angles: applications to lambda site-specific recombination complexes.
    Nucleic Acids Res. 1988 Oct 25;16(20):9687-705 PMID: 2972993
  55. In situ detection of sequence-specific DNA binding activity specified by a recombinant bacteriophage.
    Genes Dev. 1988 Jul;2(7):801-6 PMID: 3061875
  56. Flexibility of the yeast alpha 2 repressor enables it to occupy the ends of its operator, leaving the center free.
    Genes Dev. 1988 Jul;2(7):807-16 PMID: 3061876
  57. A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins.
    Cell. 1989 Mar 10;56(5):777-83 PMID: 2493990
  58. 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
  59. Identification of a transcriptional silencer in the 5'-flanking region of the human epsilon-globin gene.
    Proc Natl Acad Sci U S A. 1989 Jul;86(14):5306-9 PMID: 2748586
  60. Lethal beta-thalassaemia in mice lacking the erythroid CACCC-transcription factor EKLF.
    Nature. 1995 May 25;375(6529):318-22 PMID: 7753195
  61. Assembly and function of a TCR alpha enhancer complex is dependent on LEF-1-induced DNA bending and multiple protein-protein interactions.
    Genes Dev. 1995 Apr 15;9(8):995-1008 PMID: 7774816
  62. Activation of the TFIID-TFIIA complex with HMG-2.
    Genes Dev. 1995 Jun 1;9(11):1354-65 PMID: 7797075
  63. Inhibition of an erythroid differentiation switch by the helix-loop-helix protein Id1.
    J Biol Chem. 1995 Jul 28;270(30):17939-46 PMID: 7629100
  64. A novel developmental regulatory motif required for stage-specific activation of the epsilon-globin gene and nuclear factor binding in embryonic erythroid cells.
    Mol Cell Biol. 1994 Jun;14(6):3763-71 PMID: 8196619
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.16.3.829
Published
1996-03-00
Pages
829-38
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC231063
Subset
IM
Grants
NIGMS NIH HHS · GM 07598 · United States
NIGMS NIH HHS · R01 GM42413 · United States
NIGMS NIH HHS · R01 GM44853 · United States
External Links
PubMed source DOI: 10.1128/MCB.16.3.829 PMC Full Text View journal details
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: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2