BOP, a regulator of right ventricular heart development, is a direct transcriptional target of MEF2C in the developing heart.
The vertebrate heart is assembled during embryogenesis in a modular manner from different populations of precursor cells. The right ventricular chamber and outflow tract are derived primarily from a population of progenitors known as the anterior heart field. These regions of the heart are severely hypoplastic in mutant mice lacking the myocyte enhancer factor 2C (MEF2C) and BOP transcription factors, suggesting that these cardiogenic regulatory factors may act in a common pathway for development of the anterior heart field and its derivatives. We show that Bop expression in the developing heart depends on the direct binding of MEF2C to a MEF2-response element in the Bop promoter that is necessary and sufficient to recapitulate endogenous Bop expression in the anterior heart field and its cardiac derivatives during mouse development. The Bop promoter also directs transcription in the skeletal muscle lineage, but only cardiac expression is dependent on MEF2. These findings identify Bop as an essential downstream effector gene of MEF2C in the developing heart, and reveal a transcriptional cascade involved in development of the anterior heart field and its derivatives.
Phan
Dillon
D
Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9148, USA.
Rasmussen
Tara L
TL
Nakagawa
Osamu
O
McAnally
John
J
Gottlieb
Paul D
PD
Tucker
Philip W
PW
Richardson
James A
JA
Bassel-Duby
Rhonda
R
Olson
Eric N
EN
D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins; D024202:Electrophoretic Mobility Shift Assay; D018507:Gene Expression Regulation, Developmental; D006352:Heart Ventricles / Q000196:embryology*; D017403:In Situ Hybridization; D064326:MEF2 Transcription Factors; D051379:Mice / Q000196:embryology*; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D018006:Myogenic Regulatory Factors / Q000378:metabolism*; D009841:Oligonucleotides; D011401:Promoter Regions, Genetic / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D064326:MEF2 Transcription Factors; C578041:Mef2c protein, mouse; D009124:Muscle Proteins; D018006:Myogenic Regulatory Factors; D009841:Oligonucleotides; C096485:Smyd1 protein, mouse; D014157:Transcription Factors