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Nat Commun. 2014 May 2;5:3793. doi: 10.1038/ncomms4793.

Ebf factors and MyoD cooperate to regulate muscle relaxation via Atp2a1.

Author information

1
Institute of Clinical Molecular Biology and Tumor Genetics, Helmholtz Zentrum München, National Research Center for Environmental Health, Marchioninistrasse 25, 81377 Munich, Germany.
2
Institute of Pathology, Helmholtz Zentrum München, National Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764 Neuherberg, 81377 Munich, Germany.
3
1] Developmental Biology Section, Ecole Normale Supérieure, Rue d'Ulm 46, 75230 Paris, France [2] Stem Cells Department, CABIMER (CISC), Av Américo Vespucio, 41092 Sevilla, Spain.
4
Medical Biophysics Unit, Institute of Physiology and Pathophysiology, University of Heidelberg, Im Neuenheimer Feld 326, 69120 Heidelberg, Germany.
5
1] Institute of Pathology, Helmholtz Zentrum München, National Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764 Neuherberg, 81377 Munich, Germany [2] Institute of Pathology, Technische Universität München, Ismaningerstrasse 22, 81675 Munich, Germany.
6
Division of Endocrinology, Diabetes and Metabolic Bone Diseases, Department of Medicine III, TU Dresden Medical Center, Fetscherstrasse 74, 01307 Dresden, Germany.
7
Developmental Biology Section, Ecole Normale Supérieure, Rue d'Ulm 46, 75230 Paris, France.

Abstract

Myogenic regulatory factors such as MyoD and Myf5 lie at the core of vertebrate muscle differentiation. However, E-boxes, the cognate binding sites for these transcription factors, are not restricted to the promoters/enhancers of muscle cell-specific genes. Thus, the specificity in myogenic transcription is poorly defined. Here we describe the transcription factor Ebf3 as a new determinant of muscle cell-specific transcription. In the absence of Ebf3 the lung does not unfold at birth, resulting in respiratory failure and perinatal death. This is due to a hypercontractile diaphragm with impaired Ca(2+) efflux-related muscle functions. Expression of the Ca(2+) pump Serca1 (Atp2a1) is downregulated in the absence of Ebf3, and its transgenic expression rescues this phenotype. Ebf3 binds directly to the promoter of Atp2a1 and synergises with MyoD in the induction of Atp2a1. In skeletal muscle, the homologous family member Ebf1 is strongly expressed and together with MyoD induces Atp2a1. Thus, Ebf3 is a new regulator of terminal muscle differentiation in the diaphragm, and Ebf factors cooperate with MyoD in the induction of muscle-specific genes.

PMID:
24786561
DOI:
10.1038/ncomms4793
[Indexed for MEDLINE]
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