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Mol Cell Biol. 1994 May; 14(5): 3494–3503.
PMCID: PMC358713

Melanocyte-specific gene expression: role of repression and identification of a melanocyte-specific factor, MSF.

Abstract

For a gene to be transcribed in a tissue-specific fashion, expression must be achieved in the appropriate cell type and also be prevented in other tissues. As an approach to understanding the regulation of tissue-specific gene expression, we have analyzed the requirements for melanocyte-specific expression of the tyrosinase-related protein 1 (TRP-1) promoter. Positive regulation of TRP-1 expression is mediated by both an octamer-binding motif and an 11-bp element, termed the M box, which is conserved between the TRP-1 and other melanocyte-specific promoters. We show here that, consistent with its ability to activate transcription in a non-tissue-specific fashion, the M box binds the basic-helix-loop-helix factor USF in vitro. With the use of a combination of site-directed mutagenesis and chimeric promoter constructs, additional elements involved in regulating TRP-1 expression were identified. These include the TATA region, which appears to contribute to the melanocyte specificity of the TRP-1 promoter. Mutational analysis also identified two repressor elements, one at the start site, the other located at -240, which function both in melanoma and nonmelanoma cells. In addition, a melanocyte-specific factor, MSF, binds to sites which overlap both repressor elements, with substitution mutations demonstrating that binding by MSF is not required for repression. Although a functional role for MSF has not been unequivocally determined, the location of its binding sites leads us to speculate that it may act as a melanocyte-specific antirepressor during transcription of the endogenous TRP-1 gene.

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Selected References

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  • Ayer DE, Kretzner L, Eisenman RN. Mad: a heterodimeric partner for Max that antagonizes Myc transcriptional activity. Cell. 1993 Jan 29;72(2):211–222. [PubMed]
  • Beckmann H, Su LK, Kadesch T. TFE3: a helix-loop-helix protein that activates transcription through the immunoglobulin enhancer muE3 motif. Genes Dev. 1990 Feb;4(2):167–179. [PubMed]
  • Bennett DC. Mechanisms of differentiation in melanoma cells and melanocytes. Environ Health Perspect. 1989 Mar;80:49–59. [PMC free article] [PubMed]
  • Blackwood EM, Eisenman RN. Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc. Science. 1991 Mar 8;251(4998):1211–1217. [PubMed]
  • Carcamo J, Maldonado E, Cortes P, Ahn MH, Ha I, Kasai Y, Flint J, Reinberg D. A TATA-like sequence located downstream of the transcription initiation site is required for expression of an RNA polymerase II transcribed gene. Genes Dev. 1990 Sep;4(9):1611–1622. [PubMed]
  • Chang LA, Smith T, Pognonec P, Roeder RG, Murialdo H. Identification of USF as the ubiquitous murine factor that binds to and stimulates transcription from the immunoglobulin lambda 2-chain promoter. Nucleic Acids Res. 1992 Jan 25;20(2):287–293. [PMC free article] [PubMed]
  • Cox PM, Temperley SM, Kumar H, Goding CR. A distinct octamer-binding protein present in malignant melanoma cells. Nucleic Acids Res. 1988 Dec 9;16(23):11047–11056. [PMC free article] [PubMed]
  • Desmarais D, Filion M, Lapointe L, Royal A. Cell-specific transcription of the peripherin gene in neuronal cell lines involves a cis-acting element surrounding the TATA box. EMBO J. 1992 Aug;11(8):2971–2980. [PubMed]
  • Dignam JD, Martin PL, Shastry BS, Roeder RG. Eukaryotic gene transcription with purified components. Methods Enzymol. 1983;101:582–598. [PubMed]
  • Edmondson DG, Olson EN. Helix-loop-helix proteins as regulators of muscle-specific transcription. J Biol Chem. 1993 Jan 15;268(2):755–758. [PubMed]
  • Fisher DE, Carr CS, Parent LA, Sharp PA. TFEB has DNA-binding and oligomerization properties of a unique helix-loop-helix/leucine-zipper family. Genes Dev. 1991 Dec;5(12A):2342–2352. [PubMed]
  • Fisher F, Crouch DH, Jayaraman PS, Clark W, Gillespie DA, Goding CR. Transcription activation by Myc and Max: flanking sequences target activation to a subset of CACGTG motifs in vivo. EMBO J. 1993 Dec 15;12(13):5075–5082. [PubMed]
  • Fisher F, Goding CR. Single amino acid substitutions alter helix-loop-helix protein specificity for bases flanking the core CANNTG motif. EMBO J. 1992 Nov;11(11):4103–4109. [PubMed]
  • Fong TC, Emerson BM. The erythroid-specific protein cGATA-1 mediates distal enhancer activity through a specialized beta-globin TATA box. Genes Dev. 1992 Apr;6(4):521–532. [PubMed]
  • Gorman CM, Moffat LF, Howard BH. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. [PMC free article] [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]
  • Halazonetis TD, Kandil AN. Determination of the c-MYC DNA-binding site. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6162–6166. [PubMed]
  • Hearing VJ, Jiménez M. Mammalian tyrosinase--the critical regulatory control point in melanocyte pigmentation. Int J Biochem. 1987;19(12):1141–1147. [PubMed]
  • Hodgkinson CA, Moore KJ, Nakayama A, Steingrímsson E, Copeland NG, Jenkins NA, Arnheiter H. Mutations at the mouse microphthalmia locus are associated with defects in a gene encoding a novel basic-helix-loop-helix-zipper protein. Cell. 1993 Jul 30;74(2):395–404. [PubMed]
  • Jackson IJ, Chambers DM, Budd PS, Johnson R. The tyrosinase-related protein-1 gene has a structure and promoter sequence very different from tyrosinase. Nucleic Acids Res. 1991 Jul 25;19(14):3799–3804. [PMC free article] [PubMed]
  • Lowings P, Yavuzer U, Goding CR. Positive and negative elements regulate a melanocyte-specific promoter. Mol Cell Biol. 1992 Aug;12(8):3653–3662. [PMC free article] [PubMed]
  • McCormick A, Brady H, Fukushima J, Karin M. The pituitary-specific regulatory gene GHF1 contains a minimal cell type-specific promoter centered around its TATA box. Genes Dev. 1991 Aug;5(8):1490–1503. [PubMed]
  • Misseyanni A, Klug J, Suske G, Beato M. Novel upstream elements and the TATA-box region mediate preferential transcription from the uteroglobin promoter in endometrial cells. Nucleic Acids Res. 1991 Jun 11;19(11):2849–2859. [PMC free article] [PubMed]
  • Mitchell PJ, Tjian R. Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins. Science. 1989 Jul 28;245(4916):371–378. [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]
  • Pognonec P, Roeder RG. Recombinant 43-kDa USF binds to DNA and activates transcription in a manner indistinguishable from that of natural 43/44-kDa USF. Mol Cell Biol. 1991 Oct;11(10):5125–5136. [PMC free article] [PubMed]
  • Prendergast GC, Ziff EB. Methylation-sensitive sequence-specific DNA binding by the c-Myc basic region. Science. 1991 Jan 11;251(4990):186–189. [PubMed]
  • Roeder RG. The complexities of eukaryotic transcription initiation: regulation of preinitiation complex assembly. Trends Biochem Sci. 1991 Nov;16(11):402–408. [PubMed]
  • Roy AL, Meisterernst M, Pognonec P, Roeder RG. Cooperative interaction of an initiator-binding transcription initiation factor and the helix-loop-helix activator USF. Nature. 1991 Nov 21;354(6350):245–248. [PubMed]
  • Ruezinsky D, Beckmann H, Kadesch T. Modulation of the IgH enhancer's cell type specificity through a genetic switch. Genes Dev. 1991 Jan;5(1):29–37. [PubMed]
  • Seto E, Shi Y, Shenk T. YY1 is an initiator sequence-binding protein that directs and activates transcription in vitro. Nature. 1991 Nov 21;354(6350):241–245. [PubMed]
  • Shibahara S, Taguchi H, Muller RM, Shibata K, Cohen T, Tomita Y, Tagami H. Structural organization of the pigment cell-specific gene located at the brown locus in mouse. Its promoter activity and alternatively spliced transcript. J Biol Chem. 1991 Aug 25;266(24):15895–15901. [PubMed]
  • Smale ST, Baltimore D. The "initiator" as a transcription control element. Cell. 1989 Apr 7;57(1):103–113. [PubMed]
  • Sturm RA, Bisshop F, Takahashi H, Parsons PG. A melanoma octamer binding protein is responsive to differentiating agents. Cell Growth Differ. 1991 Oct;2(10):519–524. [PubMed]
  • Zenzie-Gregory B, O'Shea-Greenfield A, Smale ST. Similar mechanisms for transcription initiation mediated through a TATA box or an initiator element. J Biol Chem. 1992 Feb 5;267(4):2823–2830. [PubMed]
  • Zervos AS, Gyuris J, Brent R. Mxi1, a protein that specifically interacts with Max to bind Myc-Max recognition sites. Cell. 1993 Jan 29;72(2):223–232. [PubMed]

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