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Molecular and Cellular Biology, April 2004, p. 2944-2957, Vol. 24, No. 7
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.7.2944-2957.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

A Novel Complex Regulates cardiac actin Gene Expression through Interaction of Emb, a Class VI POU Domain Protein, MEF2D, and the Histone Transacetylase p300

S. Molinari,1 F. Relaix,2 M. Lemonnier,2 B. Kirschbaum,3 B. Schäfer,4 and M. Buckingham2*

CNRS URA 2578, Department of Developmental Biology, Pasteur Institute, 75724 Paris Cedex 15, France,2 Dipartimento di Scienze Biomediche, Università degli studi di Modena e Reggio Emilia, 41100 Modena, Italy,1 Aventis Pharma, D-65926 Frankfurt am Main, Germany,3 Department of Pediatrics, University of Zurich, CH-8032 Zurich, Switzerland4

Received 12 August 2002/ Returned for modification 23 October 2002/ Accepted 6 January 2004

Expression of the mouse cardiac actin gene depends on a distal enhancer (-7 kbp) which has been shown, in transgenic mice, to direct expression to embryonic skeletal muscle. The presence of this distal sequence is also associated with reproducible expression of cardiac actin transgenes. In differentiated skeletal muscle cells, activity of the enhancer is driven by an E box, binding MyoD family members, and by a 3' AT-rich sequence which is in the location of a DNase I-hypersensitive site. This sequence does not bind MEF2 proteins, or other known muscle transcription factors, directly. Oct1 and Emb, a class VI POU domain protein, bind to consensus sites on the DNA, and it is the binding of Emb which is important for activity. Emb binds as a major complex with MEF2D and the histone transacetylase p300. The form of Emb present in this complex and as a major form in muscle cell extracts is longer (80 kDa) than that previously described. These results demonstrate the importance of this novel complex in the transcriptional regulation of the cardiac actin gene and suggest a potential role in chromatin remodeling associated with muscle gene activation.


* Corresponding author. Mailing address: CNRS URA 1947, Department of Developmental Biology, Pasteur Institute, 75724 Paris Cedex 15, France. Phone: 33 1 45 68 84 77. Fax: 33 1 40 61 34 52. E-mail: margab{at}pasteur.fr.


Molecular and Cellular Biology, April 2004, p. 2944-2957, Vol. 24, No. 7
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.7.2944-2957.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.




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