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

J. Biol. Chem., Vol. 282, Issue 33, 24175-24184, August 17, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/33/24175    most recent M703746200v1 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 Inoue, K.-i. Articles by Ito, Y. Search for Related Content PubMed PubMed Citation Articles by Inoue, K.-i. Articles by Ito, Y. Social Bookmarking                      What's this?

The Transcription Factor Runx3 Represses the Neurotrophin Receptor TrkB during Lineage Commitment of Dorsal Root Ganglion Neurons^*

Ken-ichi Inoue, Kosei Ito, Motomi Osato, Bernett Lee^¶, Suk-Chul Bae^||, and Yoshiaki Ito¹

From the Institute of Molecular and Cell Biology, Singapore 13 8673, the Oncology Research Institute, National University of Singapore, and ^¶Bioinformatics Institute, Singapore, and the ^||Department of Biochemistry, School of Medicine, Institute for Tumor Research, Chungbuk National University, Cheongju 361–763, South Korea

Runx3, a Runt domain transcription factor, determines neurotrophin receptor phenotype in dorsal root ganglion (DRG) neurons. Molecular mechanisms by which Runx3 controls distinct neurotrophin receptors are largely unknown. Here, we show that RUNX3 abolished mRNA induction of TRKB expression, and concomitantly altered the neurotrophin response in a differentiating neuroblastoma cell line. In contrast, RUNX3 did not play a significant role in TRKC regulation even under the relevant BMP signaling pathway. We identified putative regulatory elements of Ntrk2/NTRK2 (a gene that codes for TrkB) using an unbiased computational approach. One of these elements was a highly conserved intronic sequence that contains a cluster of Runx binding sites. In a primary culture of DRG neurons, endogenous Runx3 bound to the consensus cluster, which had repressor activity against the Ntrk2 promoter under the control of NT-3 signaling. Consistent with these findings, Runx3-deficient embryos showed an increased number of trkB⁺ DRG neurons and failed to maintain trkC expression. Taken together, Runx3 determines TrkC positive sensory neuron identities through the transcriptional repression of TrkB when Trk-BTrkC double positive neurons differentiate into TrkC single positive neurons.

Received for publication, May 7, 2007 , and in revised form, June 15, 2007.

^* This work was supported by A^*STAR (Agency for Science, Technology and Research), Singapore. 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.

The on-line version of this article (available at http://www.jbc.org) contains a supplemental table and Fig. S.

¹ To whom correspondence should be addressed: 61 Biopolis Dr., Proteos, Singapore 138673. Tel.: 65-6586-9646; Fax: 65-6779-1117; E-mail: itoy{at}imcb.a-star.edu.sg.

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

This article has been cited by other articles:

				S. Nakamura, K. Senzaki, M. Yoshikawa, M. Nishimura, K.-i. Inoue, Y. Ito, S. Ozaki, and T. Shiga Dynamic regulation of the expression of neurotrophin receptors by Runx3 Development, May 1, 2008; 135(9): 1703 - 1711. [Abstract] [Full Text] [PDF]