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Nucleic Acids Res. Jul 25, 1991; 19(14): 3893–3899.
PMCID: PMC328480

Distribution and characterization of helix-loop-helix enhancer-binding proteins from pancreatic beta cells and lymphocytes.

Abstract

Transcription of a number of mammalian genes is controlled in part by closely-related DNA elements sharing a CAxxTG consensus sequence (E boxes). In this report, we survey cell extracts from a variety of mammalian cell lineages for ability to bind to the E box denoted IEB1/kappa E1, which plays an important role in expression of both insulin and immunoglobulin kappa genes. Insulin enhancer factor 1 (IEF1), a binding activity previously identified in beta cells, was also present in pituitary endocrine cells but absent in 7 other mammalian cell lines tested. A distinct binding activity, lymphoid enhancer factor 1 (LEF1), was observed in several lymphoid cell lines, but was absent from all nonlymphoid cells tested. IEF1 and LEF1 were distinct according to electrophoretic mobility, and DNA binding specificity. As previously reported, both beta cell and lymphoid cell factors are recognized by antibodies to helix-loop-helix (HLH) proteins, indicating that they may contain functional helix-loop-helix dimerization domains. To directly demonstrate this, we showed that the binding factors are able to interact in vitro with the HLH domain of a characterized HLH protein. These results support the notion that HLH proteins play a key role in cell-specific transcriptional regulation in cells from endocrine and lymphocyte lineages.

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Selected References

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  • Walker MD, Edlund T, Boulet AM, Rutter WJ. Cell-specific expression controlled by the 5'-flanking region of insulin and chymotrypsin genes. Nature. 1983 Dec 8;306(5943):557–561. [PubMed]
  • Edlund T, Walker MD, Barr PJ, Rutter WJ. Cell-specific expression of the rat insulin gene: evidence for role of two distinct 5' flanking elements. Science. 1985 Nov 22;230(4728):912–916. [PubMed]
  • Hanahan D. Heritable formation of pancreatic beta-cell tumours in transgenic mice expressing recombinant insulin/simian virus 40 oncogenes. Nature. 1985 May 9;315(6015):115–122. [PubMed]
  • Karlsson O, Edlund T, Moss JB, Rutter WJ, Walker MD. A mutational analysis of the insulin gene transcription control region: expression in beta cells is dependent on two related sequences within the enhancer. Proc Natl Acad Sci U S A. 1987 Dec;84(24):8819–8823. [PMC free article] [PubMed]
  • Karlsson O, Walker MD, Rutter WJ, Edlund T. Individual protein-binding domains of the insulin gene enhancer positively activate beta-cell-specific transcription. Mol Cell Biol. 1989 Feb;9(2):823–827. [PMC free article] [PubMed]
  • Whelan J, Cordle SR, Henderson E, Weil PA, Stein R. Identification of a pancreatic beta-cell insulin gene transcription factor that binds to and appears to activate cell-type-specific expression: its possible relationship to other cellular factors that bind to a common insulin gene sequence. Mol Cell Biol. 1990 Apr;10(4):1564–1572. [PMC free article] [PubMed]
  • Ohlsson H, Karlsson O, Edlund T. A beta-cell-specific protein binds to the two major regulatory sequences of the insulin gene enhancer. Proc Natl Acad Sci U S A. 1988 Jun;85(12):4228–4231. [PMC free article] [PubMed]
  • Moss LG, Moss JB, Rutter WJ. Systematic binding analysis of the insulin gene transcription control region: insulin and immunoglobulin enhancers utilize similar transactivators. Mol Cell Biol. 1988 Jun;8(6):2620–2627. [PMC free article] [PubMed]
  • Lenardo M, Pierce JW, Baltimore D. Protein-binding sites in Ig gene enhancers determine transcriptional activity and inducibility. Science. 1987 Jun 19;236(4808):1573–1577. [PubMed]
  • Lassar AB, Buskin JN, Lockshon D, Davis RL, Apone S, Hauschka SD, Weintraub H. 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):823–831. [PubMed]
  • Meister A, Weinrich SL, Nelson C, Rutter WJ. The chymotrypsin enhancer core. Specific factor binding and biological activity. J Biol Chem. 1989 Dec 5;264(34):20744–20751. [PubMed]
  • Ephrussi A, Church GM, Tonegawa S, Gilbert W. B lineage--specific interactions of an immunoglobulin enhancer with cellular factors in vivo. Science. 1985 Jan 11;227(4683):134–140. [PubMed]
  • Church GM, Ephrussi A, Gilbert W, Tonegawa S. Cell-type-specific contacts to immunoglobulin enhancers in nuclei. Nature. 313(6005):798–801. [PubMed]
  • Murre C, McCaw PS, Baltimore D. A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins. Cell. 1989 Mar 10;56(5):777–783. [PubMed]
  • Sun XH, Baltimore D. An inhibitory domain of E12 transcription factor prevents DNA binding in E12 homodimers but not in E12 heterodimers. Cell. 1991 Jan 25;64(2):459–470. [PubMed]
  • Walker MD, Park CW, Rosen A, Aronheim A. A cDNA from a mouse pancreatic beta cell encoding a putative transcription factor of the insulin gene. Nucleic Acids Res. 1990 Mar 11;18(5):1159–1166. [PMC free article] [PubMed]
  • Nelson C, Shen LP, Meister A, Fodor E, Rutter WJ. Pan: a transcriptional regulator that binds chymotrypsin, insulin, and AP-4 enhancer motifs. Genes Dev. 1990 Jun;4(6):1035–1043. [PubMed]
  • Henthorn P, Kiledjian M, Kadesch T. Two distinct transcription factors that bind the immunoglobulin enhancer microE5/kappa 2 motif. Science. 1990 Jan 26;247(4941):467–470. [PubMed]
  • Murre C, Voronova A, Baltimore D. B-cell- and myocyte-specific E2-box-binding factors contain E12/E47-like subunits. Mol Cell Biol. 1991 Feb;11(2):1156–1160. [PMC free article] [PubMed]
  • Cordle SR, Henderson E, Masuoka H, Weil PA, Stein R. Pancreatic beta-cell-type-specific transcription of the insulin gene is mediated by basic helix-loop-helix DNA-binding proteins. Mol Cell Biol. 1991 Mar;11(3):1734–1738. [PMC free article] [PubMed]
  • German MS, Blanar MA, Nelson C, Moss LG, Rutter WJ. Two related helix-loop-helix proteins participate in separate cell-specific complexes that bind the insulin enhancer. Mol Endocrinol. 1991 Feb;5(2):292–299. [PubMed]
  • Schreiber E, Matthias P, Müller MM, Schaffner W. Rapid detection of octamer binding proteins with 'mini-extracts', prepared from a small number of cells. Nucleic Acids Res. 1989 Aug 11;17(15):6419–6419. [PMC free article] [PubMed]
  • Clerc RG, Corcoran LM, LeBowitz JH, Baltimore D, Sharp PA. The B-cell-specific Oct-2 protein contains POU box- and homeo box-type domains. Genes Dev. 1988 Dec;2(12A):1570–1581. [PubMed]
  • Gregor PD, Sawadogo M, Roeder RG. The adenovirus major late transcription factor USF is a member of the helix-loop-helix group of regulatory proteins and binds to DNA as a dimer. Genes Dev. 1990 Oct;4(10):1730–1740. [PubMed]
  • Weinberger J, Baltimore D, Sharp PA. Distinct factors bind to apparently homologous sequences in the immunoglobulin heavy-chain enhancer. Nature. 322(6082):846–848. [PubMed]
  • Sen R, Baltimore D. Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell. 1986 Aug 29;46(5):705–716. [PubMed]
  • Murre C, McCaw PS, Vaessin H, Caudy M, Jan LY, Jan YN, Cabrera CV, Buskin JN, Hauschka SD, Lassar AB, et al. Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence. Cell. 1989 Aug 11;58(3):537–544. [PubMed]
  • Davis RL, Cheng PF, Lassar AB, Weintraub H. The MyoD DNA binding domain contains a recognition code for muscle-specific gene activation. Cell. 1990 Mar 9;60(5):733–746. [PubMed]
  • Benezra R, Davis RL, Lockshon D, Turner DL, Weintraub H. The protein Id: a negative regulator of helix-loop-helix DNA binding proteins. Cell. 1990 Apr 6;61(1):49–59. [PubMed]
  • Robertson M. Homoeo boxes, POU proteins and the limits to promiscuity. Nature. 1988 Dec 8;336(6199):522–524. [PubMed]
  • Renkawitz R. Transcriptional repression in eukaryotes. Trends Genet. 1990 Jun;6(6):192–197. [PubMed]
  • Lenardo MJ, Baltimore D. NF-kappa B: a pleiotropic mediator of inducible and tissue-specific gene control. Cell. 1989 Jul 28;58(2):227–229. [PubMed]
  • Müller MM, Ruppert S, Schaffner W, Matthias P. A cloned octamer transcription factor stimulates transcription from lymphoid-specific promoters in non-B cells. Nature. 1988 Dec 8;336(6199):544–551. [PubMed]
  • Scheidereit C, Cromlish JA, Gerster T, Kawakami K, Balmaceda CG, Currie RA, Roeder RG. A human lymphoid-specific transcription factor that activates immunoglobulin genes is a homoeobox protein. Nature. 1988 Dec 8;336(6199):551–557. [PubMed]
  • Staudt LM, Clerc RG, Singh H, LeBowitz JH, Sharp PA, Baltimore D. Cloning of a lymphoid-specific cDNA encoding a protein binding the regulatory octamer DNA motif. Science. 1988 Jul 29;241(4865):577–580. [PubMed]
  • Karlsson O, Thor S, Norberg T, Ohlsson H, Edlund T. Insulin gene enhancer binding protein Isl-1 is a member of a novel class of proteins containing both a homeo- and a Cys-His domain. Nature. 1990 Apr 26;344(6269):879–882. [PubMed]

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