Ebf factors and MyoD cooperate to regulate muscle relaxation via Atp2a1

• Published in: Nature communications Vol. 5; no. 1; p. 3793
• Main Authors: Jin, Saihong, Kim, Jeehee, Willert, Torsten, Klein-Rodewald, Tanja, Garcia-Dominguez, Mario, Mosqueira, Matias, Fink, Rainer, Esposito, Irene, Hofbauer, Lorenz C., Charnay, Patrick, Kieslinger, Matthias
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.05.2014; Nature Publishing Group
• Subjects: 13/31; 38/15; 38/22; 38/44; 38/71; 38/90; 42/109; 42/41; 631/136; 631/337; 64/60; 692/698/1671/1668; 82; Animals; Humanities and Social Sciences; Mice; Mice, Knockout; multidisciplinary; Muscle Relaxation - physiology; MyoD Protein - physiology; Respiratory Insufficiency - genetics; Sarcoplasmic Reticulum Calcium-Transporting ATPases - genetics; Sarcoplasmic Reticulum Calcium-Transporting ATPases - physiology; Science; Science (multidisciplinary); Transcription Factors - physiology
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms4793

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. The specificity in myogenic transcription is poorly defined. Here, Jin et al . describe Ebf3 as a regulator of terminal muscle differentiation in the diaphragm and show that Ebf factors cooperate with the myogenic regulatory factor MyoD in the induction of muscle-specific genes.