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. 1992 Aug;11(8):2971–2980. doi: 10.1002/j.1460-2075.1992.tb05367.x

Cell-specific transcription of the peripherin gene in neuronal cell lines involves a cis-acting element surrounding the TATA box.

D Desmarais 1, M Filion 1, L Lapointe 1, A Royal 1
PMCID: PMC556779  PMID: 1639068

Abstract

Peripherin is a neurone-specific intermediate filament protein expressed mostly in the peripheral nervous system. To localize sequences that are important for the regulation of peripherin gene transcription, we have functionally dissected its promoter. Transfection into different cell lines and deletion mapping of peripherin-lacZ hybrid constructs indicated that the first 98 bp preceding the transcription start site of the gene were sufficient to confer cell-type specific expression. DNase I footprinting experiments revealed three protected sequences in this region, that were named PER1, PER2 and PER3. The PER2 and PER3 elements, localized between -98 to -46, interact with proteins that seem widely distributed. Deletion of these elements severely decreased the level of reporter gene activity. The PER1 element, which overlaps the TATA box, interacts with a DNA-binding protein prevailing in peripherin expressing cell lines. However, the core promoter, which contains the PER1 element, was inefficient in driving gene expression. Experiments designed to test the contribution of each element showed that PER2 and PER3 were important in determining the level of expression, while PER1 was important for cell-type specificity. In fact the polyoma virus enhancer linked to the peripherin gene core promoter was found to limit reporter gene activity to peripherin expressing cell lines. Together, these experiments indicate that co-operative interactions between different regions of the promoter are necessary for efficient and cell-type specific transcription of the peripherin gene in a subset of neuronal cells.

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  1. Auffray C., Rougeon F. Purification of mouse immunoglobulin heavy-chain messenger RNAs from total myeloma tumor RNA. Eur J Biochem. 1980 Jun;107(2):303–314. doi: 10.1111/j.1432-1033.1980.tb06030.x. [DOI] [PubMed] [Google Scholar]
  2. Bennett G. S., DiLullo C. Transient expression of a neurofilament protein by replicating neuroepithelial cells of the embryonic chick brain. Dev Biol. 1985 Jan;107(1):107–127. doi: 10.1016/0012-1606(85)90380-x. [DOI] [PubMed] [Google Scholar]
  3. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  4. Brody B. A., Ley C. A., Parysek L. M. Selective distribution of the 57 kDa neural intermediate filament protein in the rat CNS. J Neurosci. 1989 Jul;9(7):2391–2401. doi: 10.1523/JNEUROSCI.09-07-02391.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Carlow D. A., Kerbel R. S., Feltis J. T., Elliott B. E. Enhanced expression of class I major histocompatibility complex gene (Dk) products on immunogenic variants of a spontaneous murine carcinoma. J Natl Cancer Inst. 1985 Aug;75(2):291–301. [PubMed] [Google Scholar]
  6. Ching G. Y., Liem R. K. Structure of the gene for the neuronal intermediate filament protein alpha-internexin and functional analysis of its promoter. J Biol Chem. 1991 Oct 15;266(29):19459–19468. [PubMed] [Google Scholar]
  7. Davidson I., Xiao J. H., Rosales R., Staub A., Chambon P. The HeLa cell protein TEF-1 binds specifically and cooperatively to two SV40 enhancer motifs of unrelated sequence. Cell. 1988 Sep 23;54(7):931–942. doi: 10.1016/0092-8674(88)90108-0. [DOI] [PubMed] [Google Scholar]
  8. Dierks P., van Ooyen A., Cochran M. D., Dobkin C., Reiser J., Weissmann C. Three regions upstream from the cap site are required for efficient and accurate transcription of the rabbit beta-globin gene in mouse 3T6 cells. Cell. 1983 Mar;32(3):695–706. doi: 10.1016/0092-8674(83)90055-7. [DOI] [PubMed] [Google Scholar]
  9. Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dynlacht B. D., Hoey T., Tjian R. Isolation of coactivators associated with the TATA-binding protein that mediate transcriptional activation. Cell. 1991 Aug 9;66(3):563–576. doi: 10.1016/0092-8674(81)90019-2. [DOI] [PubMed] [Google Scholar]
  11. Edlund T., Walker M. D., Barr P. J., Rutter W. J. 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. doi: 10.1126/science.3904002. [DOI] [PubMed] [Google Scholar]
  12. Escurat M., Djabali K., Gumpel M., Gros F., Portier M. M. Differential expression of two neuronal intermediate-filament proteins, peripherin and the low-molecular-mass neurofilament protein (NF-L), during the development of the rat. J Neurosci. 1990 Mar;10(3):764–784. doi: 10.1523/JNEUROSCI.10-03-00764.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fliegner K. H., Ching G. Y., Liem R. K. The predicted amino acid sequence of alpha-internexin is that of a novel neuronal intermediate filament protein. EMBO J. 1990 Mar;9(3):749–755. doi: 10.1002/j.1460-2075.1990.tb08169.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Fromental C., Kanno M., Nomiyama H., Chambon P. Cooperativity and hierarchical levels of functional organization in the SV40 enhancer. Cell. 1988 Sep 23;54(7):943–953. doi: 10.1016/0092-8674(88)90109-2. [DOI] [PubMed] [Google Scholar]
  15. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Greene L. A. A new neuronal intermediate filament protein. Trends Neurosci. 1989 Jun;12(6):228–230. doi: 10.1016/0166-2236(89)90127-6. [DOI] [PubMed] [Google Scholar]
  17. Greene L. A., Tischler A. S. Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor. Proc Natl Acad Sci U S A. 1976 Jul;73(7):2424–2428. doi: 10.1073/pnas.73.7.2424. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hobson G. M., Mitchell M. T., Molloy G. R., Pearson M. L., Benfield P. A. Identification of a novel TA-rich DNA binding protein that recognizes a TATA sequence within the brain creatine kinase promoter. Nucleic Acids Res. 1988 Sep 26;16(18):8925–8944. doi: 10.1093/nar/16.18.8925. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Horlick R. A., Hobson G. M., Patterson J. H., Mitchell M. T., Benfield P. A. Brain and muscle creatine kinase genes contain common TA-rich recognition protein-binding regulatory elements. Mol Cell Biol. 1990 Sep;10(9):4826–4836. doi: 10.1128/mcb.10.9.4826. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kaneko T., LePage G. A. Growth characteristics and drug responses of a murine lung carcinoma in vitro and in vivo. Cancer Res. 1978 Jul;38(7):2084–2090. [PubMed] [Google Scholar]
  21. Landon F., Lemonnier M., Benarous R., Huc C., Fiszman M., Gros F., Portier M. M. Multiple mRNAs encode peripherin, a neuronal intermediate filament protein. EMBO J. 1989 Jun;8(6):1719–1726. doi: 10.1002/j.1460-2075.1989.tb03564.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lathe R., Vilotte J. L., Clark A. J. Plasmid and bacteriophage vectors for excision of intact inserts. Gene. 1987;57(2-3):193–201. doi: 10.1016/0378-1119(87)90122-3. [DOI] [PubMed] [Google Scholar]
  23. Lendahl U., Zimmerman L. B., McKay R. D. CNS stem cells express a new class of intermediate filament protein. Cell. 1990 Feb 23;60(4):585–595. doi: 10.1016/0092-8674(90)90662-x. [DOI] [PubMed] [Google Scholar]
  24. Leonard D. G., Gorham J. D., Cole P., Greene L. A., Ziff E. B. A nerve growth factor-regulated messenger RNA encodes a new intermediate filament protein. J Cell Biol. 1988 Jan;106(1):181–193. doi: 10.1083/jcb.106.1.181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Leonard D. G., Ziff E. B., Greene L. A. Identification and characterization of mRNAs regulated by nerve growth factor in PC12 cells. Mol Cell Biol. 1987 Sep;7(9):3156–3167. doi: 10.1128/mcb.7.9.3156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Lussier M., Ouellet T., Lampron C., Lapointe L., Royal A. Mouse keratin 19: complete amino acid sequence and gene expression during development. Gene. 1989 Dec 28;85(2):435–444. doi: 10.1016/0378-1119(89)90437-x. [DOI] [PubMed] [Google Scholar]
  27. Maxam A. M., Gilbert W. A new method for sequencing DNA. Proc Natl Acad Sci U S A. 1977 Feb;74(2):560–564. doi: 10.1073/pnas.74.2.560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  29. Minna J., Glazer D., Nirenberg M. Genetic dissection of neural properties using somatic cell hybrids. Nat New Biol. 1972 Feb 23;235(60):225–231. doi: 10.1038/newbio235225a0. [DOI] [PubMed] [Google Scholar]
  30. Miura M., Tamura T., Mikoshiba K. Cell-specific expression of the mouse glial fibrillary acidic protein gene: identification of the cis- and trans-acting promoter elements for astrocyte-specific expression. J Neurochem. 1990 Oct;55(4):1180–1188. doi: 10.1111/j.1471-4159.1990.tb03123.x. [DOI] [PubMed] [Google Scholar]
  31. Myers R. M., Tilly K., Maniatis T. Fine structure genetic analysis of a beta-globin promoter. Science. 1986 May 2;232(4750):613–618. doi: 10.1126/science.3457470. [DOI] [PubMed] [Google Scholar]
  32. Nakajima N., Horikoshi M., Roeder R. G. Factors involved in specific transcription by mammalian RNA polymerase II: purification, genetic specificity, and TATA box-promoter interactions of TFIID. Mol Cell Biol. 1988 Oct;8(10):4028–4040. doi: 10.1128/mcb.8.10.4028. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Nelson P., Christian C., Nirenberg M. Synapse formation between clonal neuroblastoma X glioma hybrid cells and striated muscle cells. Proc Natl Acad Sci U S A. 1976 Jan;73(1):123–127. doi: 10.1073/pnas.73.1.123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Parysek L. M., Chisholm R. L., Ley C. A., Goldman R. D. A type III intermediate filament gene is expressed in mature neurons. Neuron. 1988 Jul;1(5):395–401. doi: 10.1016/0896-6273(88)90189-4. [DOI] [PubMed] [Google Scholar]
  35. Parysek L. M., Goldman R. D. Characterization of intermediate filaments in PC12 cells. J Neurosci. 1987 Mar;7(3):781–791. doi: 10.1523/JNEUROSCI.07-03-00781.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Parysek L. M., Goldman R. D. Distribution of a novel 57 kDa intermediate filament (IF) protein in the nervous system. J Neurosci. 1988 Feb;8(2):555–563. doi: 10.1523/JNEUROSCI.08-02-00555.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Pevny L., Simon M. C., Robertson E., Klein W. H., Tsai S. F., D'Agati V., Orkin S. H., Costantini F. Erythroid differentiation in chimaeric mice blocked by a targeted mutation in the gene for transcription factor GATA-1. Nature. 1991 Jan 17;349(6306):257–260. doi: 10.1038/349257a0. [DOI] [PubMed] [Google Scholar]
  38. Portier M. M., Brachet P., Croizat B., Gros F. Regulation of peripherin in mouse neuroblastoma and rat PC 12 pheochromocytoma cell lines. Dev Neurosci. 1983;6(4-5):215–226. doi: 10.1159/000112348. [DOI] [PubMed] [Google Scholar]
  39. Portier M. M., Croizat B., Gros F. A sequence of changes in cytoskeletal components during neuroblastoma differentiation. FEBS Lett. 1982 Sep 20;146(2):283–288. doi: 10.1016/0014-5793(82)80935-6. [DOI] [PubMed] [Google Scholar]
  40. Portier M. M., de Néchaud B., Gros F. Peripherin, a new member of the intermediate filament protein family. Dev Neurosci. 1983;6(6):335–344. doi: 10.1159/000112360. [DOI] [PubMed] [Google Scholar]
  41. Quax W., Egberts W. V., Hendriks W., Quax-Jeuken Y., Bloemendal H. The structure of the vimentin gene. Cell. 1983 Nov;35(1):215–223. doi: 10.1016/0092-8674(83)90224-6. [DOI] [PubMed] [Google Scholar]
  42. Quax W., van den Broek L., Egberts W. V., Ramaekers F., Bloemendal H. Characterization of the hamster desmin gene: expression and formation of desmin filaments in nonmuscle cells after gene transfer. Cell. 1985 Nov;43(1):327–338. doi: 10.1016/0092-8674(85)90038-8. [DOI] [PubMed] [Google Scholar]
  43. Richet E., Raibaud O. MalT, the regulatory protein of the Escherichia coli maltose system, is an ATP-dependent transcriptional activator. EMBO J. 1989 Mar;8(3):981–987. doi: 10.1002/j.1460-2075.1989.tb03461.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Richet E., Vidal-Ingigliardi D., Raibaud O. A new mechanism for coactivation of transcription initiation: repositioning of an activator triggered by the binding of a second activator. Cell. 1991 Sep 20;66(6):1185–1195. doi: 10.1016/0092-8674(91)90041-v. [DOI] [PubMed] [Google Scholar]
  45. Rittling S. R., Baserga R. Functional analysis and growth factor regulation of the human vimentin promoter. Mol Cell Biol. 1987 Nov;7(11):3908–3915. doi: 10.1128/mcb.7.11.3908. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Ryder E. F., Snyder E. Y., Cepko C. L. Establishment and characterization of multipotent neural cell lines using retrovirus vector-mediated oncogene transfer. J Neurobiol. 1990 Mar;21(2):356–375. doi: 10.1002/neu.480210209. [DOI] [PubMed] [Google Scholar]
  47. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Sawadogo M., Sentenac A. RNA polymerase B (II) and general transcription factors. Annu Rev Biochem. 1990;59:711–754. doi: 10.1146/annurev.bi.59.070190.003431. [DOI] [PubMed] [Google Scholar]
  49. Schüle R., Muller M., Kaltschmidt C., Renkawitz R. Many transcription factors interact synergistically with steroid receptors. Science. 1988 Dec 9;242(4884):1418–1420. doi: 10.1126/science.3201230. [DOI] [PubMed] [Google Scholar]
  50. Schüle R., Muller M., Otsuka-Murakami H., Renkawitz R. Cooperativity of the glucocorticoid receptor and the CACCC-box binding factor. Nature. 1988 Mar 3;332(6159):87–90. doi: 10.1038/332087a0. [DOI] [PubMed] [Google Scholar]
  51. Simon M. C., Rooney R. J., Fisch T. M., Heintz N., Nevins J. R. E1A-dependent trans-activation of the c-fos promoter requires the TATAA sequence. Proc Natl Acad Sci U S A. 1990 Jan;87(2):513–517. doi: 10.1073/pnas.87.2.513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Solomon M. J., Strauss F., Varshavsky A. A mammalian high mobility group protein recognizes any stretch of six A.T base pairs in duplex DNA. Proc Natl Acad Sci U S A. 1986 Mar;83(5):1276–1280. doi: 10.1073/pnas.83.5.1276. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Steinert P. M., Roop D. R. Molecular and cellular biology of intermediate filaments. Annu Rev Biochem. 1988;57:593–625. doi: 10.1146/annurev.bi.57.070188.003113. [DOI] [PubMed] [Google Scholar]
  54. Sykes J. A., Whitescarver J., Jernstrom P., Nolan J. F., Byatt P. Some properties of a new epithelial cell line of human origin. J Natl Cancer Inst. 1970 Jul;45(1):107–122. [PubMed] [Google Scholar]
  55. Tapscott S. J., Bennett G. S., Holtzer H. Neuronal precursor cells in the chick neural tube express neurofilament proteins. Nature. 1981 Aug 27;292(5826):836–838. doi: 10.1038/292836a0. [DOI] [PubMed] [Google Scholar]
  56. Taylor I. C., Kingston R. E. Factor substitution in a human HSP70 gene promoter: TATA-dependent and TATA-independent interactions. Mol Cell Biol. 1990 Jan;10(1):165–175. doi: 10.1128/mcb.10.1.165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Thomas K. R., Capecchi M. R. Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells. Cell. 1987 Nov 6;51(3):503–512. doi: 10.1016/0092-8674(87)90646-5. [DOI] [PubMed] [Google Scholar]
  58. Thompson M. A., Ziff E. B. Structure of the gene encoding peripherin, an NGF-regulated neuronal-specific type III intermediate filament protein. Neuron. 1989 Jan;2(1):1043–1053. doi: 10.1016/0896-6273(89)90228-6. [DOI] [PubMed] [Google Scholar]
  59. Timmers H. T., Sharp P. A. The mammalian TFIID protein is present in two functionally distinct complexes. Genes Dev. 1991 Nov;5(11):1946–1956. doi: 10.1101/gad.5.11.1946. [DOI] [PubMed] [Google Scholar]
  60. Troy C. M., Muma N. A., Greene L. A., Price D. L., Shelanski M. L. Regulation of peripherin and neurofilament expression in regenerating rat motor neurons. Brain Res. 1990 Oct 8;529(1-2):232–238. doi: 10.1016/0006-8993(90)90832-v. [DOI] [PubMed] [Google Scholar]
  61. Walker M. D., Edlund T., Boulet A. M., Rutter W. J. Cell-specific expression controlled by the 5'-flanking region of insulin and chymotrypsin genes. Nature. 1983 Dec 8;306(5943):557–561. doi: 10.1038/306557a0. [DOI] [PubMed] [Google Scholar]
  62. Wang W. D., Gralla J. D. Differential ability of proximal and remote element pairs to cooperate in activating RNA polymerase II transcription. Mol Cell Biol. 1991 Sep;11(9):4561–4571. doi: 10.1128/mcb.11.9.4561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Wefald F. C., Devlin B. H., Williams R. S. Functional heterogeneity of mammalian TATA-box sequences revealed by interaction with a cell-specific enhancer. Nature. 1990 Mar 15;344(6263):260–262. doi: 10.1038/344260a0. [DOI] [PubMed] [Google Scholar]
  64. Weintraub H., Davis R., Tapscott S., Thayer M., Krause M., Benezra R., Blackwell T. K., Turner D., Rupp R., Hollenberg S. The myoD gene family: nodal point during specification of the muscle cell lineage. Science. 1991 Feb 15;251(4995):761–766. doi: 10.1126/science.1846704. [DOI] [PubMed] [Google Scholar]
  65. Wong J., Oblinger M. M. Differential regulation of peripherin and neurofilament gene expression in regenerating rat DRG neurons. J Neurosci Res. 1990 Nov;27(3):332–341. doi: 10.1002/jnr.490270312. [DOI] [PubMed] [Google Scholar]

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