Abstract
A DNA-binding factor with high affinity and specificity for the [Leu5]enkephalin-encoding sequences in the prodynorphin and proenkephalin genes has been characterized. The factor has the highest affinity for the [Leu5]-enkephalin-encoding sequence in the dynorphin B-encoding region of the prodynorphin gene, has relatively high affinity for other [Leu5]enkephalin-encoding sequences in the prodynorphin and proenkephalin genes, but has no apparent affinity for similar DNA sequences coding for [Met5]-enkephalin in the prodynorphin or proopiomelanocortin genes. The factor has been named [Leu5]enkephalin-encoding sequence DNA-binding factor (LEF). LEF has a nuclear localization and is composed of three subunits of about 60, 70, and 95 kDa, respectively. The highest levels were observed in rat testis, cerebellum, and spleen and were generally higher in late embryonal compared to newborn or adult animals. LEF activity was also recorded in human clonal tumor cell lines. LEF inhibited the transcription of reporter genes in artificial gene constructs where a [Leu5]enkephalin-encoding DNA fragment had been inserted between the transcription initiation site and the coding region of the reporter genes. These observations suggest that the [Leu5]enkephalin-encoding sequences in the prodynorphin and proenkephalin genes also have regulatory functions realized through interaction with a specific DNA-binding factor.
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- Akil H., Watson S. J., Young E., Lewis M. E., Khachaturian H., Walker J. M. Endogenous opioids: biology and function. Annu Rev Neurosci. 1984;7:223–255. doi: 10.1146/annurev.ne.07.030184.001255. [DOI] [PubMed] [Google Scholar]
- Baeuerle P. A., Baltimore D. Activation of DNA-binding activity in an apparently cytoplasmic precursor of the NF-kappa B transcription factor. Cell. 1988 Apr 22;53(2):211–217. doi: 10.1016/0092-8674(88)90382-0. [DOI] [PubMed] [Google Scholar]
- Bakalkin GYa, Yakovleva T., Terenius L. NF-kappa B-like factors in the murine brain. Developmentally-regulated and tissue-specific expression. Brain Res Mol Brain Res. 1993 Oct;20(1-2):137–146. doi: 10.1016/0169-328x(93)90119-a. [DOI] [PubMed] [Google Scholar]
- Bakalkin G., Yakovleva T., Terenius L. Prodynorphin gene expression relates to NF-kappa B factors. Brain Res Mol Brain Res. 1994 Jul;24(1-4):301–312. doi: 10.1016/0169-328x(94)90143-0. [DOI] [PubMed] [Google Scholar]
- Collins-Hicok J., Lin L., Spiro C., Laybourn P. J., Tschumper R., Rapacz B., McMurray C. T. Induction of the rat prodynorphin gene through Gs-coupled receptors may involve phosphorylation-dependent derepression and activation. Mol Cell Biol. 1994 May;14(5):2837–2848. doi: 10.1128/mcb.14.5.2837. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Comb M., Seeburg P. H., Adelman J., Eiden L., Herbert E. Primary structure of the human Met- and Leu-enkephalin precursor and its mRNA. Nature. 1982 Feb 25;295(5851):663–666. doi: 10.1038/295663a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Douglass J., McKinzie A. A., Pollock K. M. Identification of multiple DNA elements regulating basal and protein kinase A-induced transcriptional expression of the rat prodynorphin gene. Mol Endocrinol. 1994 Mar;8(3):333–344. doi: 10.1210/mend.8.3.8015551. [DOI] [PubMed] [Google Scholar]
- Faisst S., Meyer S. Compilation of vertebrate-encoded transcription factors. Nucleic Acids Res. 1992 Jan 11;20(1):3–26. doi: 10.1093/nar/20.1.3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Franklin G. C., Donovan M., Adam G. I., Holmgren L., Pfeifer-Ohlsson S., Ohlsson R. Expression of the human PDGF-B gene is regulated by both positively and negatively acting cell type-specific regulatory elements located in the first intron. EMBO J. 1991 Jun;10(6):1365–1373. doi: 10.1002/j.1460-2075.1991.tb07656.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Geijer T., Bergh J., Terenius L. Expression of preprodynorphin in human small cell lung carcinoma cell lines. Regul Pept. 1991 Jul 9;34(3):181–188. doi: 10.1016/0167-0115(91)90177-i. [DOI] [PubMed] [Google Scholar]
- Greenblatt J., Nodwell J. R., Mason S. W. Transcriptional antitermination. Nature. 1993 Jul 29;364(6436):401–406. doi: 10.1038/364401a0. [DOI] [PubMed] [Google Scholar]
- Horikawa S., Takai T., Toyosato M., Takahashi H., Noda M., Kakidani H., Kubo T., Hirose T., Inayama S., Hayashida H. Isolation and structural organization of the human preproenkephalin B gene. Nature. 1983 Dec 8;306(5943):611–614. doi: 10.1038/306611a0. [DOI] [PubMed] [Google Scholar]
- Ishiguro H., Kim K. T., Joh T. H., Kim K. S. Neuron-specific expression of the human dopamine beta-hydroxylase gene requires both the cAMP-response element and a silencer region. J Biol Chem. 1993 Aug 25;268(24):17987–17994. [PubMed] [Google Scholar]
- Kaneko K. J., Furlow J. D., Gorski J. Involvement of the coding sequence for the estrogen receptor gene in autologous ligand-dependent down-regulation. Mol Endocrinol. 1993 Jul;7(7):879–888. doi: 10.1210/mend.7.7.8413312. [DOI] [PubMed] [Google Scholar]
- Lauster R., Reynaud C. A., Mårtensson I. L., Peter A., Bucchini D., Jami J., Weill J. C. Promoter, enhancer and silencer elements regulate rearrangement of an immunoglobulin transgene. EMBO J. 1993 Dec;12(12):4615–4623. doi: 10.1002/j.1460-2075.1993.tb06150.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lucas J. J., Mellström B., Colado M. I., Naranjo J. R. Molecular mechanisms of pain: serotonin1A receptor agonists trigger transactivation by c-fos of the prodynorphin gene in spinal cord neurons. Neuron. 1993 Apr;10(4):599–611. doi: 10.1016/0896-6273(93)90163-l. [DOI] [PubMed] [Google Scholar]
- Martens G. J. Expression of two proopiomelanocortin genes in the pituitary gland of Xenopus laevis: complete structures of the two preprohormones. Nucleic Acids Res. 1986 May 12;14(9):3791–3798. doi: 10.1093/nar/14.9.3791. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Messersmith D. J., Gu J., Dubner R., Douglass J., Iadarola M. J. Basal and inducible transcriptional activity of an upstream AP-1/CRE element (DYNCRE3) in the prodynorphin promoter. Mol Cell Neurosci. 1994 Jun;5(3):238–245. doi: 10.1006/mcne.1994.1028. [DOI] [PubMed] [Google Scholar]
- Müller M. M., Gerster T., Schaffner W. Enhancer sequences and the regulation of gene transcription. Eur J Biochem. 1988 Oct 1;176(3):485–495. doi: 10.1111/j.1432-1033.1988.tb14306.x. [DOI] [PubMed] [Google Scholar]
- Naranjo J. R., Mellström B., Achaval M., Sassone-Corsi P. Molecular pathways of pain: Fos/Jun-mediated activation of a noncanonical AP-1 site in the prodynorphin gene. Neuron. 1991 Apr;6(4):607–617. doi: 10.1016/0896-6273(91)90063-6. [DOI] [PubMed] [Google Scholar]
- Rougvie A. E., Lis J. T. The RNA polymerase II molecule at the 5' end of the uninduced hsp70 gene of D. melanogaster is transcriptionally engaged. Cell. 1988 Sep 9;54(6):795–804. doi: 10.1016/s0092-8674(88)91087-2. [DOI] [PubMed] [Google Scholar]
- Schoenherr C. J., Anderson D. J. The neuron-restrictive silencer factor (NRSF): a coordinate repressor of multiple neuron-specific genes. Science. 1995 Mar 3;267(5202):1360–1363. doi: 10.1126/science.7871435. [DOI] [PubMed] [Google Scholar]
- Spencer C. A., Groudine M. Transcription elongation and eukaryotic gene regulation. Oncogene. 1990 Jun;5(6):777–785. [PubMed] [Google Scholar]
- Takahashi H., Teranishi Y., Nakanishi S., Numa S. Isolation and structural organization of the human corticotropin--beta-lipotropin precursor gene. FEBS Lett. 1981 Nov 30;135(1):97–102. doi: 10.1016/0014-5793(81)80952-0. [DOI] [PubMed] [Google Scholar]
- Udenfriend S., Kilpatrick D. L. Biochemistry of the enkephalins and enkephalin-containing peptides. Arch Biochem Biophys. 1983 Mar;221(2):309–323. doi: 10.1016/0003-9861(83)90149-2. [DOI] [PubMed] [Google Scholar]
- Wissmann A., Hillen W. DNA contacts probed by modification protection and interference studies. Methods Enzymol. 1991;208:365–379. doi: 10.1016/0076-6879(91)08020-i. [DOI] [PubMed] [Google Scholar]
- Wong M., Rius R. A., Loh Y. P. Characterization of Xenopus laevis proenkephalin gene. Brain Res Mol Brain Res. 1991 Oct;11(3-4):197–205. doi: 10.1016/0169-328x(91)90028-v. [DOI] [PubMed] [Google Scholar]