Skip to main content

Neuronal Gene Regulation by the Neural — Restrictive Silencer (NRS)

Is the catecholaminergic system excluded from control by NRS?

  • Chapter
Catecholamine Research

Part of the book series: Advances in Behavioral Biology ((ABBI,volume 53))

  • 19 Accesses

Abstract

Neural restrictive silencer (NRS) is a 22-bp-long cell type-specific transcriptional silencer element that is found in a variety of neural-specific genes.1,2 NRS represses transcription in non-neuronal cells, thereby allowing gene expression only in neurons. The sequence-specific DNA-binding protein that recognizes NRS (NRSF, also named REST) is expressed essentially in undifferentiated neuronal precursors and non-neuronal cells and functions as a transcriptional repressor.3 NRSF represents the first example of a vertebrate silencer factor that regulates a large battery of neuronal phenotype-specific genes, and therefore may function as a general negative regulator of neuronal terminal differentiation. However, in contrast to what was originally thought, recent evidence suggests that NRS is found in many genes involved in the cholinergic, GABAergic, and glutamatergic neuronal transmission, but may not be evident in the genes that relate to monoaminergic neurotransmission. Here I would like to discuss the possibility that NRS represses neurons to acquire monoaminergic function and that the role of NRS could be somehow limited in monoaminergic or catecholaminergic systems.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. C. J. Schoenherr, D. J Anderson. Silencing is golden: negative regulation in the control of neuronal gene transcription. Curr. Opin. Neurobiol. 5, 566–571 (1995).

    Article  PubMed  CAS  Google Scholar 

  2. K. Miyaguchi, Y. Maeda, T. Kojima, Y. Setoguchi, N. Mori, Neuron-targeted gene transfer by adenovirus carrying neural-restrictive silencer element. Neuroreport 10, 2349–2353 (1999).

    Article  PubMed  CAS  Google Scholar 

  3. J. A. Chong, J. Tapia-Ramirez, S. Kim, J. J. Toledo-Aral, Y. Zheng, M. C. Boutros, Y. M. Altshuller, M. A. Frohman, S. D. Kraner, G. Mandel, REST: a mammalian silencer protein that restricts sodium channel gene expression to neurons. Cell 80, 949–957 (1995).

    Article  PubMed  CAS  Google Scholar 

  4. Z. F. Chen, A. J. Paquette, D. J. Anderson, NRSF/REST is required in vivo for repression of multiple neuronal target genes during embryogenesis. Nature Genet. 20, 136–142 (1998).

    Article  PubMed  CAS  Google Scholar 

  5. A. J. Paquette, S. E. Perez, D. J. Anderson, Constitutive expression of the NRSF/REST in differentiating neurons disrupts neuronal gene expression and causes axon pathfinding errors in vivo. Proc. Natl. Acad. Sci. U S A 97, 12318–12323 (2000).

    Article  PubMed  CAS  Google Scholar 

  6. N. Mori, Neural-restrictive silencer (NRS) and its regulatory factor NRSF/REST, Exp. Med. (in Japanese) 15, 446–454(1997)

    CAS  Google Scholar 

  7. M. E. Andres, C. Burger, M. J. Peral-Rubio, E. Battaglioli, M. E. Anderson, J. Grimes, J. Dallman, N. Ballas, and G. Mandel, CoREST: a functional corepressor required for regulation of neural-specific gene expression. Proc. Natl. Acad. Sci. U S A 96, 9873–9878 (1999).

    Article  PubMed  CAS  Google Scholar 

  8. Y. Naruse, T. Aoki, T. Kojima, N. Mori, NRSF recruits mSin3 and histone deacetylase complex to repress neuron-specific target genes. . Proc. Natl. Acad. Sci. USA 96, 13691–13696 (1999).

    Article  PubMed  CAS  Google Scholar 

  9. Y. Huang, S. J. Myers, R. Dingledine, Transcriptional repression by REST: recruitment of Sin3A and histone deacetylase to neuronal genes. Nature Neurosci. 2, 867–872 (1999).

    Article  PubMed  CAS  Google Scholar 

  10. A. Roopra, L. Shading, I. C. Wood, T. Briggs, U. Bachfischer, A. J. Paquette, N. J. Buckley, Transcriptional repression by NRSF is mediated via the Sin3-histone deacetylase complex. Mol. Cell Biol. 20, 2147–2157 (2000).

    Article  PubMed  CAS  Google Scholar 

  11. H. Ishiguro, K. S. Kim, T. H. Joh, Identification of a negative regulatory element in the 5’-flanking region of the human dopamine beta-hydroxylase gene. Brain Res. Mol. Brain Res. 34, 251–261 (1995).

    Article  CAS  Google Scholar 

  12. J. J. Schimmel, L. Crew, S. Roffler-Tarlov, and D. M. Chikaraichi, 4.5 kb of the rat tyrosine hydroxylase 5’ flanking sequence directs tissue specific expression during development and contains consensus sites for multiple transcription factors, Mol. Brain Res. 74, 1–14 (1999).

    Article  CAS  Google Scholar 

  13. C. Koenigsberger, J. J. Chicca, M. C. Amoureux, G. M. Edelman, F. S. Jones, Differential regulation by multiple promoters of the gene encoding the NRSF. Proc. Natl. Acad. Sci. USA 97, 2291–2296 (2000).

    Article  PubMed  CAS  Google Scholar 

  14. T. Kojima, K. Murai, Y. Naruse, N. Takahashi, and N. Mori, Cell-type non-selective transcription of mouse and human genes encoding NRSF, Mol. Brain Res. 90, 174–186 (2001)

    Article  PubMed  CAS  Google Scholar 

  15. K. Palm, N. Belluardo, M. Metsis, T. Timmusk, Neuronal expression of zinc finger transcription factor REST/NRSF/XBR gene. J. Neurosci. 18, 1280–1296 (1998).

    PubMed  CAS  Google Scholar 

  16. M. Shimojo, A. J. Paquette, D. J. Anderson, L. B. Hersh, Protein kinase Aregulates cholinergic gene expression in PC12 Cells: REST4 silences the silencing activity of NRSF/REST. Mol. Cell. Biol. 19, 6788–6795 (1999).

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2002 Springer Science+Business Media New York

About this chapter

Cite this chapter

Mori, N. (2002). Neuronal Gene Regulation by the Neural — Restrictive Silencer (NRS). In: Nagatsu, T., Nabeshima, T., McCarty, R., Goldstein, D.S. (eds) Catecholamine Research. Advances in Behavioral Biology, vol 53. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-3538-3_47

Download citation

  • DOI: https://doi.org/10.1007/978-1-4757-3538-3_47

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4419-3388-1

  • Online ISBN: 978-1-4757-3538-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics