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PMID: 1312219 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

HEB, a helix-loop-helix protein related to E2A and ITF2 that can modulate the DNA-binding ability of myogenic regulatory factors.

Molecular and cellular biology ·Vol. 12 ·No. 3 ·1992-03-00 ·Pages 1031-42

Hu JS, Olson EN, Kingston RE

Abstract

Proteins containing the basic-helix-loop-helix (B-HLH) domain have been shown to be important in regulating cellular differentiation. We have isolated a cDNA for a human B-HLH factor, denoted HEB, that shares nearly complete identity in the B-HLH domain with the immunoglobulin enhancer binding proteins encoded by the E2A and ITF2 genes (E proteins). Functional characterization of the protein expressed from this cDNA indicates that HEB is a third member of the E-protein class of B-HLH factors. HEB mRNA was found to be expressed in several tissues and cell types, including skeletal muscle, thymus, and a B-cell line. HEB, ITF2, and the E12 product of the E2A gene all bound to a similar spectrum of E-box sequences as homo-oligomers. All three factors also formed hetero-oligomers with myogenin, and the DNA-binding specificity and binding off-rates (dissociation rates) were modulated after hetero-oligomerization. Both homo- and hetero-oligomers of these proteins were able to distinguish between very closely related E-box sequences. In addition, HEB was shown to form hetero-oligomers with the E12 and ITF2 proteins. Finally, HEB was able to activate gene expression. These data demonstrate that HEB shares characteristics with other E proteins and show that HEB can interact with members of both the myogenic regulatory class and the E-protein class of B-HLH factors. HEB is therefore likely to play an important role in regulating lineage-specific gene expression.

MeSH Terms
Amino Acid Sequence Base Sequence Basic Helix-Loop-Helix Transcription Factors Binding Sites DNA/metabolism DNA-Binding Proteins/genetics,metabolism Gene Expression Regulation Humans Molecular Sequence Data Muscle Proteins/metabolism Myogenin Organ Specificity/genetics Precipitin Tests Sequence Alignment TCF Transcription Factors Trans-Activators/genetics,metabolism Transcription Factor 7-Like 1 Protein Transcription Factors Tumor Cells, Cultured
Chemicals
Basic Helix-Loop-Helix Transcription Factors DNA-Binding Proteins MYOG protein, human Muscle Proteins Myogenin TCF Transcription Factors TCF7L1 protein, human Trans-Activators Transcription Factor 7-Like 1 Protein Transcription Factors TCF12 protein, human DNA
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Hu J S
Department of Genetics, Harvard Medical School, Boston, Massachusetts.
Olson E N
Kingston R E
References (45)
45 references, click to expand
  1. Functional activity of myogenic HLH proteins requires hetero-oligomerization with E12/E47-like proteins in vivo.
    Cell. 1991 Jul 26;66(2):305-15 PMID: 1649701
  2. The muscle creatine kinase gene is regulated by multiple upstream elements, including a muscle-specific enhancer.
    Mol Cell Biol. 1988 Jan;8(1):62-70 PMID: 3336366
  3. Inefficient homooligomerization contributes to the dependence of myogenin on E2A products for efficient DNA binding.
    Mol Cell Biol. 1991 Jul;11(7):3633-41 PMID: 1646392
  4. Cyclic amplification and selection of targets (CASTing) for the myogenin consensus binding site.
    Mol Cell Biol. 1991 Aug;11(8):4104-10 PMID: 1649388
  5. Muscle-specific expression of the troponin I gene requires interactions between helix-loop-helix muscle regulatory factors and ubiquitous transcription factors.
    Mol Cell Biol. 1991 Jan;11(1):267-80 PMID: 1846022
  6. Identification of upstream and intragenic regulatory elements that confer cell-type-restricted and differentiation-specific expression on the muscle creatine kinase gene.
    Mol Cell Biol. 1988 Jul;8(7):2896-909 PMID: 3405222
  7. Expression of a single transfected cDNA converts fibroblasts to myoblasts.
    Cell. 1987 Dec 24;51(6):987-1000 PMID: 3690668
  8. B lineage--specific interactions of an immunoglobulin enhancer with cellular factors in vivo.
    Science. 1985 Jan 11;227(4683):134-40 PMID: 3917574
  9. Cell-type-specific contacts to immunoglobulin enhancers in nuclei.
    Nature. 1985 Feb 28-Mar 6;313(6005):798-801 PMID: 3919308
  10. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity.
    Anal Biochem. 1983 Jul 1;132(1):6-13 PMID: 6312838
  11. An inhibitory domain of E12 transcription factor prevents DNA binding in E12 homodimers but not in E12 heterodimers.
    Cell. 1991 Jan 25;64(2):459-70 PMID: 1846322
  12. The myoD gene family: nodal point during specification of the muscle cell lineage.
    Science. 1991 Feb 15;251(4995):761-6 PMID: 1846704
  13. Differential trans-activation of a muscle-specific enhancer by myogenic helix-loop-helix proteins is separable from DNA binding.
    J Biol Chem. 1991 Feb 15;266(5):2878-82 PMID: 1847137
  14. Paired MyoD-binding sites regulate myosin light chain gene expression.
    Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1242-6 PMID: 1847512
  15. Heterodimers of myogenic helix-loop-helix regulatory factors and E12 bind a complex element governing myogenic induction of the avian cardiac alpha-actin promoter.
    Mol Cell Biol. 1991 May;11(5):2439-50 PMID: 1850096
  16. HTF4: a new human helix-loop-helix protein.
    Nucleic Acids Res. 1991 Aug 25;19(16):4555 PMID: 1886779
  17. A new homeobox gene contributes the DNA binding domain of the t(1;19) translocation protein in pre-B ALL.
    Cell. 1990 Feb 23;60(4):547-55 PMID: 1967983
  18. Two distinct transcription factors that bind the immunoglobulin enhancer microE5/kappa 2 motif.
    Science. 1990 Jan 26;247(4941):467-70 PMID: 2105528
  19. Mutations that disrupt DNA binding and dimer formation in the E47 helix-loop-helix protein map to distinct domains.
    Proc Natl Acad Sci U S A. 1990 Jun;87(12):4722-6 PMID: 2112746
  20. Muscle-specific expression of the cardiac alpha-actin gene requires MyoD1, CArG-box binding factor, and Sp1.
    Genes Dev. 1990 Oct;4(10):1811-22 PMID: 2123467
  21. The MyoD DNA binding domain contains a recognition code for muscle-specific gene activation.
    Cell. 1990 Mar 9;60(5):733-46 PMID: 2155707
  22. The protein Id: a negative regulator of helix-loop-helix DNA binding proteins.
    Cell. 1990 Apr 6;61(1):49-59 PMID: 2156629
  23. Myogenin resides in the nucleus and acquires high affinity for a conserved enhancer element on heterodimerization.
    Genes Dev. 1990 Apr;4(4):582-95 PMID: 2163343
  24. Differences and similarities in DNA-binding preferences of MyoD and E2A protein complexes revealed by binding site selection.
    Science. 1990 Nov 23;250(4984):1104-10 PMID: 2174572
  25. Pan: a transcriptional regulator that binds chymotrypsin, insulin, and AP-4 enhancer motifs.
    Genes Dev. 1990 Jun;4(6):1035-43 PMID: 2200736
  26. A highly conserved enhancer downstream of the human MLC1/3 locus is a target for multiple myogenic determination factors.
    Nucleic Acids Res. 1990 Nov 11;18(21):6239-46 PMID: 2243772
  27. MyoD family: a paradigm for development?
    Genes Dev. 1990 Sep;4(9):1454-61 PMID: 2253873
  28. Herculin, a fourth member of the MyoD family of myogenic regulatory genes.
    Proc Natl Acad Sci U S A. 1990 Feb;87(3):1089-93 PMID: 2300571
  29. Myf-6, a new member of the human gene family of myogenic determination factors: evidence for a gene cluster on chromosome 12.
    EMBO J. 1990 Mar;9(3):821-31 PMID: 2311584
  30. Two adjacent MyoD1-binding sites regulate expression of the acetylcholine receptor alpha-subunit gene.
    Nature. 1990 May 24;345(6273):353-5 PMID: 2342565
  31. MyoD binds cooperatively to two sites in a target enhancer sequence: occupancy of two sites is required for activation.
    Proc Natl Acad Sci U S A. 1990 Aug;87(15):5623-7 PMID: 2377600
  32. Transcriptional activation domain of the muscle-specific gene-regulatory protein myf5.
    Nature. 1990 Aug 16;346(6285):663-5 PMID: 2385294
  33. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
    Anal Biochem. 1987 Apr;162(1):156-9 PMID: 2440339
  34. A gene with homology to the myc similarity region of MyoD1 is expressed during myogenesis and is sufficient to activate the muscle differentiation program.
    Genes Dev. 1989 May;3(5):628-40 PMID: 2473006
  35. 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
  36. Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence.
    Cell. 1989 Aug 11;58(3):537-44 PMID: 2503252
  37. Myogenin, a factor regulating myogenesis, has a domain homologous to MyoD.
    Cell. 1989 Feb 24;56(4):607-17 PMID: 2537150
  38. MyoD is a sequence-specific DNA binding protein requiring a region of myc homology to bind to the muscle creatine kinase enhancer.
    Cell. 1989 Sep 8;58(5):823-31 PMID: 2550138
  39. Identification of MRF4: a new member of the muscle regulatory factor gene family.
    Genes Dev. 1989 Dec;3(12B):2050-61 PMID: 2560751
  40. Molecular cloning of sequence-specific DNA binding proteins using recognition site probes.
    Biotechniques. 1989 Mar;7(3):252-61 PMID: 2698648
  41. A novel human muscle factor related to but distinct from MyoD1 induces myogenic conversion in 10T1/2 fibroblasts.
    EMBO J. 1989 Mar;8(3):701-9 PMID: 2721498
  42. In situ detection of sequence-specific DNA binding activity specified by a recombinant bacteriophage.
    Genes Dev. 1988 Jul;2(7):801-6 PMID: 3061875
  43. Protein-binding sites in Ig gene enhancers determine transcriptional activity and inducibility.
    Science. 1987 Jun 19;236(4808):1573-7 PMID: 3109035
  44. Identification and characterization of two functional domains within the murine heavy-chain enhancer.
    Mol Cell Biol. 1988 Jan;8(1):145-52 PMID: 3122021
  45. Helix-loop-helix transcription factor E47 activates germ-line immunoglobulin heavy-chain gene transcription and rearrangement in a pre-T-cell line.
    Genes Dev. 1991 Aug;5(8):1367-76 PMID: 1714414
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.12.3.1031-1042.1992
Published
1992-03-00
Pages
1031-42
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC369535
Subset
IM
Databases
GENBANK
M80627
External Links
PubMed source DOI: 10.1128/mcb.12.3.1031-1042.1992 PMC Full Text View journal details
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