Skip to main content
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1995 Jan;15(1):246–254. doi: 10.1128/mcb.15.1.246

The maf proto-oncogene stimulates transcription from multiple sites in a promoter that directs Purkinje neuron-specific gene expression.

C Kurschner 1, J I Morgan 1
PMCID: PMC231945  PMID: 7799931

Abstract

L7 is expressed in all adult cerebellar Purkinje cells, although during development it appears in a stereotyped spatial and temporal pattern that is manifested as parasagittal domains of neurons. Mutations of the L7 promoter in transgenic mice have established that these domains represent functional compartments of Purkinje neurons. Therefore, it is hoped that by defining the transcriptional control of the L7 gene insights into the mechanisms that control functional fate and organization in the nervous system can be gained. Fragments of the L7 promoter were introduced into a selectable reporter gene in Saccharomyces cerevisiae, and these strains were used to select for cerebellar cDNAs encoding proteins that can bind to, and activate transcription from, these elements. This assay identified the c-Maf proto-oncogene as activating transcription from two sites in the L7 promoter. We did a functional domain analysis of vertebrate c-Maf based upon transcriptional activation in S. cerevisiae and showed the requirement for a transactivation domain, leucine zipper, and DNA-binding region in c-Maf. The c-Maf interaction site was mapped to the sequence G/TGG/CNG/TNCT CAGNN in the L7 promoter, which represents an atypical 12-O-tetradecanoate-13-acetate-responsive element-type Maf-responsive element. However, neither Fos nor Jun, either alone or in combination with each other or c-Maf, altered transcription from this element. In contrast, a Maf-related protein, Nrl, completely mimicked c-Maf actions. These data suggest that Maf may interact with additional basic-zipper proteins that determine a subtype of Maf-responsive element binding.

Full Text

The Full Text of this article is available as a PDF (339.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andrews N. C., Kotkow K. J., Ney P. A., Erdjument-Bromage H., Tempst P., Orkin S. H. The ubiquitous subunit of erythroid transcription factor NF-E2 is a small basic-leucine zipper protein related to the v-maf oncogene. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11488–11492. doi: 10.1073/pnas.90.24.11488. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Berrebi A. S., Oberdick J., Sangameswaran L., Christakos S., Morgan J. I., Mugnaini E. Cerebellar Purkinje cell markers are expressed in retinal bipolar neurons. J Comp Neurol. 1991 Jun 22;308(4):630–649. doi: 10.1002/cne.903080409. [DOI] [PubMed] [Google Scholar]
  3. Dalton S., Treisman R. Characterization of SAP-1, a protein recruited by serum response factor to the c-fos serum response element. Cell. 1992 Feb 7;68(3):597–612. doi: 10.1016/0092-8674(92)90194-h. [DOI] [PubMed] [Google Scholar]
  4. Fields S., Song O. A novel genetic system to detect protein-protein interactions. Nature. 1989 Jul 20;340(6230):245–246. doi: 10.1038/340245a0. [DOI] [PubMed] [Google Scholar]
  5. Fujiwara K. T., Kataoka K., Nishizawa M. Two new members of the maf oncogene family, mafK and mafF, encode nuclear b-Zip proteins lacking putative trans-activator domain. Oncogene. 1993 Sep;8(9):2371–2380. [PubMed] [Google Scholar]
  6. Guarente L., Ptashne M. Fusion of Escherichia coli lacZ to the cytochrome c gene of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2199–2203. doi: 10.1073/pnas.78.4.2199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hoffman C. S., Winston F. A ten-minute DNA preparation from yeast efficiently releases autonomous plasmids for transformation of Escherichia coli. Gene. 1987;57(2-3):267–272. doi: 10.1016/0378-1119(87)90131-4. [DOI] [PubMed] [Google Scholar]
  8. Igarashi K., Kataoka K., Itoh K., Hayashi N., Nishizawa M., Yamamoto M. Regulation of transcription by dimerization of erythroid factor NF-E2 p45 with small Maf proteins. Nature. 1994 Feb 10;367(6463):568–572. doi: 10.1038/367568a0. [DOI] [PubMed] [Google Scholar]
  9. Ito H., Fukuda Y., Murata K., Kimura A. Transformation of intact yeast cells treated with alkali cations. J Bacteriol. 1983 Jan;153(1):163–168. doi: 10.1128/jb.153.1.163-168.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kataoka K., Nishizawa M., Kawai S. Structure-function analysis of the maf oncogene product, a member of the b-Zip protein family. J Virol. 1993 Apr;67(4):2133–2141. doi: 10.1128/jvi.67.4.2133-2141.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kataoka K., Noda M., Nishizawa M. Maf nuclear oncoprotein recognizes sequences related to an AP-1 site and forms heterodimers with both Fos and Jun. Mol Cell Biol. 1994 Jan;14(1):700–712. doi: 10.1128/mcb.14.1.700. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kerppola T. K., Curran T. Maf and Nrl can bind to AP-1 sites and form heterodimers with Fos and Jun. Oncogene. 1994 Mar;9(3):675–684. [PubMed] [Google Scholar]
  13. Nishizawa M., Kataoka K., Goto N., Fujiwara K. T., Kawai S. v-maf, a viral oncogene that encodes a "leucine zipper" motif. Proc Natl Acad Sci U S A. 1989 Oct;86(20):7711–7715. doi: 10.1073/pnas.86.20.7711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Oberdick J., Schilling K., Smeyne R. J., Corbin J. G., Bocchiaro C., Morgan J. I. Control of segment-like patterns of gene expression in the mouse cerebellum. Neuron. 1993 Jun;10(6):1007–1018. doi: 10.1016/0896-6273(93)90050-2. [DOI] [PubMed] [Google Scholar]
  15. Oberdick J., Smeyne R. J., Mann J. R., Zackson S., Morgan J. I. A promoter that drives transgene expression in cerebellar Purkinje and retinal bipolar neurons. Science. 1990 Apr 13;248(4952):223–226. doi: 10.1126/science.2109351. [DOI] [PubMed] [Google Scholar]
  16. Sangameswaran L., Morgan J. I. Structure and regulation of the gene encoding the neuron-specific protein PEP-19. Brain Res Mol Brain Res. 1993 Jul;19(1-2):62–68. doi: 10.1016/0169-328x(93)90149-j. [DOI] [PubMed] [Google Scholar]
  17. Smeyne R. J., Oberdick J., Schilling K., Berrebi A. S., Mugnaini E., Morgan J. I. Dynamic organization of developing Purkinje cells revealed by transgene expression. Science. 1991 Nov 1;254(5032):719–721. doi: 10.1126/science.1948052. [DOI] [PubMed] [Google Scholar]
  18. Swaroop A., Xu J. Z., Pawar H., Jackson A., Skolnick C., Agarwal N. A conserved retina-specific gene encodes a basic motif/leucine zipper domain. Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):266–270. doi: 10.1073/pnas.89.1.266. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Wang M. M., Reed R. R. Molecular cloning of the olfactory neuronal transcription factor Olf-1 by genetic selection in yeast. Nature. 1993 Jul 8;364(6433):121–126. doi: 10.1038/364121a0. [DOI] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES