QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online November 18, 2003
doi: 10.1242/10.1242/jcs.00824

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted 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 Kelly, R. G. Articles by Buckingham, M. E. Search for Related Content PubMed PubMed Citation Articles by Kelly, R. G. Articles by Buckingham, M. E. Social Bookmarking                         What's this?

Cell history determines the maintenance of transcriptional differences between left and right ventricular cardiomyocytes in the developing mouse heart

Robert G. Kelly^*,, Marguerite Lemonnier, Stephane Zaffran, Andrew Munk and Margaret E. Buckingham

CNRS URA 2578, Department of Developmental Biology, Pasteur Institute, 25 Rue du Dr Roux, Paris 75015, France

Authors for correspondence (e-mail: margab{at}pasteur.fr; rkelly{at}pasteur.fr)

Accepted 6 August 2003

The molecular mechanisms that establish and maintain transcriptional differences between cardiomyocytes in the left and right ventricular chambers are unkown. We have previously analysed a myosin light chain 3f transgene containing an nlacZ reporter gene, which is transcribed in left but not right ventricular cardiomyocytes. In this report we examine the mechanisms involved in maintaining regionalised transgene expression. Primary cardiomyocytes prepared from left and right ventricular walls of transgenic mice were found to maintain transgene expression status in culture. However, similar cultures prepared from nontransgenic mice or rats show uniform expression after transient transfection of Mlc3f constructs, suggesting that the mechanism responsible for differential expression of the transgene between left and right ventricular cells does not operate on transiently introduced molecules. These data suggest that developmental cell history determines transgene expression status. Maintenance of transgene expression status is regulated by a cell-autonomous mechanism that is independent of DNA methylation, trichostatin A-sensitive histone deacetylation and miss-expression of transcription factors that are expressed in the left or right ventricles of the embryonic heart. Parallels between Mlc3f transgene repression in right ventricular cardiomyocytes and polycomb-mediated silencing in Drosophila suggest that Mlc3f regulatory sequences included on the transgene may contain a cellular memory module that is switched into an on or off state during early cardiogenesis. Epigenetic mechanisms may therefore be involved in maintaining patterning of the mammalian myocardium.

Key words: Cardiomyocytes, Transcriptional repression, Transgenic mice

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

This article has been cited by other articles:

				S. S. Jonker, L. Zhang, S. Louey, G. D. Giraud, K. L. Thornburg, and J. J. Faber Myocyte enlargement, differentiation, and proliferation kinetics in the fetal sheep heart J Appl Physiol, March 1, 2007; 102(3): 1130 - 1142. [Abstract] [Full Text] [PDF]

				M. Lemonnier and M. E. Buckingham Characterization of a Cardiac-specific Enhancer, Which Directs {alpha}-Cardiac Actin Gene Transcription in the Mouse Adult Heart J. Biol. Chem., December 31, 2004; 279(53): 55651 - 55658. [Abstract] [Full Text] [PDF]