This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow An erratum has been published
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Su, X.
Right arrow Articles by Majumder, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Su, X.
Right arrow Articles by Majumder, S.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, September 2004, p. 8018-8025, Vol. 24, No. 18
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.18.8018-8025.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Activation of REST/NRSF Target Genes in Neural Stem Cells Is Sufficient To Cause Neuronal Differentiation

Xiaohua Su,1,{dagger} Sei Kameoka,1,{ddagger} Susan Lentz,1 and Sadhan Majumder2,3*

Department of Molecular Genetics,1 Brain Tumor Center, University of Texas M. D. Anderson Cancer Center,2 Program in Genes and Development, University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas3

Received 27 February 2004/ Returned for modification 27 April 2004/ Accepted 21 June 2004

REST/NRSF is a transcriptional repressor that acts at the terminal stage of the neuronal differentiation pathway and blocks the transcription of several differentiation genes. REST/NRSF is generally downregulated during induction of neuronal differentiation. The recombinant transcription factor REST-VP16 binds to the same DNA binding site as does REST/NRSF but functions as an activator instead of a repressor and can directly activate the transcription of REST/NRSF target genes. However, it is not known whether REST-VP16 expression is sufficient to cause formation of functional neurons from neural stem cells (NSCs). Here we show that regulated expression of REST-VP16 in a physiologically relevant NSC line growing under cycling conditions converted the cells rapidly to the mature neuronal phenotype. Furthermore, when grown in the presence of retinoic acid, REST-VP16-expressing NSCs activated their target, as well as other differentiation genes that are not their direct target, converting them to the mature neuronal phenotype and enabling them to survive in the presence of mitotic inhibitors, which is a characteristic of mature neurons. In addition, these neuronal cells were physiologically active. These results showed that direct activation of REST/NRSF target genes in NSCs with a single transgene, REST-VP16, is sufficient to cause neuronal differentiation, and the findings suggested that direct activation of genes involved in the terminal stage of differentiation may cause neuronal differentiation of NSCs.

* Corresponding author. Mailing address: University of Texas M. D. Anderson Cancer Center, Molecular Genetics, 1515 Holcombe Blvd., Unit 11, Houston, TX 77030. Phone: (713) 792-8920. Fax: (713) 792-6054. E-mail: majumder{at}mdanderson.org.

{dagger} Present address: Department of Pediatrics and Genetic Medicine, The Johns Hopkins University, Baltimore, MD 21205.

{ddagger} Present address: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138.

Molecular and Cellular Biology, September 2004, p. 8018-8025, Vol. 24, No. 18
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.18.8018-8025.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Theodorou, E., Dalembert, G., Heffelfinger, C., White, E., Weissman, S., Corcoran, L., Snyder, M. (2009). A high throughput embryonic stem cell screen identifies Oct-2 as a bifunctional regulator of neuronal differentiation. Genes Dev. 23: 575-588 [Abstract] [Full Text]  
  • Kagalwala, M.N., Singh, S.K., Majumder, S. (2009). Stemness Is Only a State of the Cell. Cold Spring Harb Symp Quant Biol 0: sqb.2008.73.042v1-sqb.2008.73.042 [Abstract]  
  • Ekici, M., Hohl, M., Schuit, F., Martinez-Serrano, A., Thiel, G. (2008). Transcription of Genes Encoding Synaptic Vesicle Proteins in Human Neural Stem Cells: CHROMATIN ACCESSIBILITY, HISTONE METHYLATION PATTERN, AND THE ESSENTIAL ROLE OF REST. J. Biol. Chem. 283: 9257-9268 [Abstract] [Full Text]  
  • Greenway, D. J., Street, M., Jeffries, A., Buckley, N. J. (2007). RE1 Silencing Transcription Factor Maintains a Repressive Chromatin Environment in Embryonic Hippocampal Neural Stem Cells. Stem Cells 25: 354-363 [Abstract] [Full Text]  
  • Ooi, L., Belyaev, N. D., Miyake, K., Wood, I. C., Buckley, N. J. (2006). BRG1 Chromatin Remodeling Activity Is Required for Efficient Chromatin Binding by Repressor Element 1-silencing Transcription Factor (REST) and Facilitates REST-mediated Repression. J. Biol. Chem. 281: 38974-38980 [Abstract] [Full Text]  
  • Su, X., Gopalakrishnan, V., Stearns, D., Aldape, K., Lang, F. F., Fuller, G., Snyder, E., Eberhart, C. G., Majumder, S. (2006). Abnormal Expression of REST/NRSF and Myc in Neural Stem/Progenitor Cells Causes Cerebellar Tumors by Blocking Neuronal Differentiation.. Mol. Cell. Biol. 26: 1666-1678 [Abstract] [Full Text]  
  • Kurschat, P., Bielenberg, D., Rossignol-Tallandier, M., Stahl, A., Klagsbrun, M. (2006). Neuron Restrictive Silencer Factor NRSF/REST Is a Transcriptional Repressor of Neuropilin-1 and Diminishes the Ability of Semaphorin 3A to Inhibit Keratinocyte Migration. J. Biol. Chem. 281: 2721-2729 [Abstract] [Full Text]  
  • Sun, Y.-M., Greenway, D. J., Johnson, R., Street, M., Belyaev, N. D., Deuchars, J., Bee, T., Wilde, S., Buckley, N. J. (2005). Distinct Profiles of REST Interactions with Its Target Genes at Different Stages of Neuronal Development. Mol. Biol. Cell 16: 5630-5638 [Abstract] [Full Text]  
  • Ovcharenko, I., Nobrega, M. A. (2005). Identifying synonymous regulatory elements in vertebrate genomes. Nucleic Acids Res 33: W403-W407 [Abstract] [Full Text]  
  • Fuller, G. N., Su, X., Price, R. E., Cohen, Z. R., Lang, F. F., Sawaya, R., Majumder, S. (2005). Many human medulloblastoma tumors overexpress repressor element-1 silencing transcription (REST)/neuron-restrictive silencer factor, which can be functionally countered by REST-VP16. Molecular Cancer Therapeutics 4: 343-349 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»