HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 283, Issue 14, 9257-9268, April 4, 2008

This Article Full Text Full Text (PDF) All Versions of this Article: 283/14/9257    most recent M709388200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ekici, M. Articles by Thiel, G. Search for Related Content PubMed PubMed Citation Articles by Ekici, M. Articles by Thiel, G. Social Bookmarking                      What's this?

Transcription of Genes Encoding Synaptic Vesicle Proteins in Human Neural Stem Cells

CHROMATIN ACCESSIBILITY, HISTONE METHYLATION PATTERN, AND THE ESSENTIAL ROLE OF REST^*

Myriam Ekici, Mathias Hohl, Frans Schuit, Alberto Martínez-Serrano^¶, and Gerald Thiel¹

From the Department of Medical Biochemistry and Molecular Biology, University of Saarland Medical Center, D-66421 Homburg, Germany, the Department of Molecular Cell Biology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium, and the ^¶Center of Molecular Biology Severo Ochoa, CSIC-UAM, Cantoblanco, 28049 Madrid, Spain

Human HNSC.100 neural stem cells up-regulate expression of GFAP following withdrawal of mitogens. Activation of the ERK signaling pathway prevented the up-regulation of GFAP expression. Incubation of cells with retinoic acid in the absence of mitogens enhanced basal neuronal differentiation that was accompanied by an up-regulation of neuronal gene expression and a down-regulation of GFAP and nestin expression. Retinoic acid treatment changed the histone code of neuronal genes encoding synapsin I, synaptophysin, and synaptotagmins II, IV, and VII from a transcriptionally inactive (methylation of lysine residue 9 of histone 3) to a transcriptionally active state (methylation of lysine residue 4 of histone 3). In contrast, the chromatin structure of the GFAP gene is transformed from a transcriptionally active state in unstimulated neural stem cells to a transcriptionally inactive state in retinoic acid-stimulated cells. Additionally, retinoic acid treatment reduced the binding of histone deacetylase-1 and REST to neuronal genes. The inhibition of histone deacetylase activity induced expression of genes encoding synaptic vesicle proteins in unstimulated neural stem cells. Similarly, neuronal gene transcription was enhanced following expression of a mutant of REST that contained a transcriptional activation domain. These data indicate that in undifferentiated human neural stem cells, neuronal genes encoding synaptic vesicle proteins are accessible for the REST mutant and are sensitive to enhanced histone acetylation.

Received for publication, November 15, 2007 , and in revised form, January 29, 2008.

^* This work was supported in part by a grant from the Zentrale Forschungskommison der Universität des Saarlandes (2006) and HOMFOR (B/2004/38). The work at the Center of Molecular Biology Severo Ochoa was supported by grants from the following Spanish Agencies: Ministerio de Educacíon y Ciencia Project SAF 2004-03405, Foundation La Caixa BM05-20, Instituto de Salud Carlos III, RD06/0010/0009, and the institutional grant to the Centro de Biología Molecular Severo Ochoa from the Foundation Ramon Areces. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Dept. of Medical Biochemistry and Molecular Biology, Bldg. 44, University of Saarland Medical Center, D-66421 Homburg, Germany. Tel.: 49-6841-1626506; Fax: 49-6841-1626500; E-mail: gerald.thiel{at}uniklinik-saarland.de.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. B. Wu, K. Chen, X.-M. Ou, and J. C. Shih Retinoic Acid Activates Monoamine Oxidase B Promoter in Human Neuronal Cells J. Biol. Chem., June 19, 2009; 284(25): 16723 - 16735. [Abstract] [Full Text] [PDF]

				A. Golebiewska, S. P. Atkinson, M. Lako, and L. Armstrong Epigenetic Landscaping During hESC Differentiation to Neural Cells Stem Cells, June 1, 2009; 27(6): 1298 - 1308. [Abstract] [Full Text] [PDF]