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

J. Biol. Chem., Vol. 281, Issue 19, 13604-13611, May 12, 2006

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 281/19/13604    most recent M513278200v1 Alert me when this article is cited 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bai, S. Articles by Jacob, S. T. Search for Related Content PubMed PubMed Citation Articles by Bai, S. Articles by Jacob, S. T. Social Bookmarking                      What's this?

Identification of T-cadherin as a Novel Target of DNA Methyltransferase 3B and Its Role in the Suppression of Nerve Growth Factor-mediated Neurite Outgrowth in PC12 Cells^*

From the Department of Molecular and Cellular Biochemistry, College of Medicine, Ohio State University, Columbus, Ohio 43210

Previously we showed that DNA methyltransferase 3b (Dnmt3b) is required for nerve growth factor (NGF)-induced differentiation of PC12 cells to neuronal phenotype. The present study identified T-cadherin (T-Cad) as one of the targets of Dnmt3b by chromatin immunoprecipitation (ChIP) assay. Combined bisulfite restriction analysis and bisulfite sequencing showed that T-Cad promoter was sparsely methylated in PC12 cells. ChIP-CHOP analysis demonstrated that Dnmt3b is associated with T-Cad promoter irrespective of its methylation status. The mRNA and protein levels of T-Cad were markedly elevated in cells depleted of Dnmt3b by antisense or small interfering RNA. Suppression of T-Cad promoter activity by Dnmt3b was independent of its catalytic activity, which was consistent with the insignificant change in T-Cad promoter methylation status in Dnmt3b-depleted cells. In contrast, deletion of its N-terminal ATRX and PWWP domain abolished its repressor function. Association of histone deacetylase 2 (Hdac2) with T-Cad promoter and restoration of the promoter activity from Dnmt3b-mediated suppression upon treatment with Hdac inhibitor indicated involvement of histone deacetylation in this process. NGF-induced neurite outgrowth was inhibited in a dose dependent manner upon ectopic expression of T-Cad in PC12 cells. Immunofluorescence studies showed that T-Cad was redistributed upon NGF treatment, as evident from its concentration in axon growth cones as opposed to its localization at cell-cell contact region in undifferentiated cells. These results demonstrate a novel role of T-Cad in the NGF-mediated differentiation of PC12 cells to neuronal phenotype.

Received for publication, December 13, 2005 , and in revised form, March 14, 2006.

^* This work was supported in part by Grants ES 10874, and CA 86978 (to S. T. J.), from the National Institutes of Health. 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 supplemental Table S1.

¹ To whom correspondence should be addressed: Dept. of Molecular and Cellular Biochemistry, College of Medicine, Ohio State University, 333 Hamilton Hall, 1645 Neil Ave., Columbus, OH 43210. Tel.: 614-688-5494; Fax: 614-688-5600; E-mail: jacob.42{at}osu.edu.

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

This article has been cited by other articles:

				S. Bai, J. Datta, S. T. Jacob, and K. Ghoshal Treatment of PC12 Cells with Nerve Growth Factor Induces Proteasomal Degradation of T-cadherin That Requires Tyrosine Phosphorylation of Its Cadherin Domain J. Biol. Chem., September 14, 2007; 282(37): 27171 - 27180. [Abstract] [Full Text] [PDF]