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

J. Biol. Chem., Vol. 282, Issue 35, 25748-25759, August 31, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/35/25748    most recent M703724200v1 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 Farin, H. F. Articles by Kispert, A. Search for Related Content PubMed PubMed Citation Articles by Farin, H. F. Articles by Kispert, A. Related Collections Papers Of The Week Social Bookmarking                      What's this?

Transcriptional Repression by the T-box Proteins Tbx18 and Tbx15 Depends on Groucho Corepressors^*

From the Institute for Molecular Biology, Medizinische Hochschule Hannover, 30625 Hannover, Germany

Tbox18 (Tbx18) and Tbox15 (Tbx15) encode a closely related pair of vertebrate-specific T-box (Tbx) transcription factors. Functional analyses in the mouse have proven the requirement of Tbx15 in skin and skeletal development and of Tbx18 in the formation of the vertebral column, the ureter, and the posterior pole of the heart. Despite the accumulation of genetic data concerning the embryological roles of these genes, it is currently unclear how Tbx18 and Tbx15 exert their function on the molecular level. Here, we have initiated a molecular analysis of Tbx18 and Tbx15 proteins and have characterized functional domains for nuclear localization, DNA binding, and transcriptional modulation. We show that both proteins homo- and heterodimerize, bind to various combinations of T half-sites, and repress transcription in a Groucho-dependent manner. Competition with activating T-box proteins may constitute one mode of action as we show that Tbx18 interacts with Gata4 and Nkx2-5 and competes Tbx5-mediated activation of the cardiac Natriuretic peptide precursor type a-promoter and that ectopic expression of Tbx18 down-regulates Tbx6-activated Delta-like 1 expression in the somitic mesoderm in vivo.

Received for publication, May 4, 2007 , and in revised form, June 21, 2007.

^* This work was supported by a grant from the European Union FP6 contract "HeartRepair" (LSHM-CT-2005-018630), by grants from the German Research Council (DFG) and by the DFG-funded cluster of excellence "REBIRTH." 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.

This article was selected as a Paper of the Week.

¹ To whom correspondence should be addressed: Medizinische Hochschule Hannover, Institute for Molecular Biology, OE5250, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany. Tel.: 49-511-5324017; Fax: 49-511-5324283; E-mail: kispert.andreas{at}mh-hannover.de.

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

This article has been cited by other articles:

				K. E. Yutzey Teed Off: Cardiac Conduction System Development Requires T-box Transcription Factors Circ. Res., June 6, 2008; 102(11): 1295 - 1297. [Full Text] [PDF]

				K.-J. Boogerd, L.Y. E. Wong, V. M. Christoffels, M. Klarenbeek, J. M. Ruijter, A. F.M. Moorman, and P. Barnett Msx1 and Msx2 are functional interacting partners of T-box factors in the regulation of Connexin43 Cardiovasc Res, June 1, 2008; 78(3): 485 - 493. [Abstract] [Full Text] [PDF]