title: Myocardin is sufficient and necessary for cardiac gene expression in Xenopus.
abstract: Myocardin is a cardiac- and smooth muscle-specific cofactor for the ubiquitous transcription factor serum response factor (SRF). Using gain-of-function approaches in the Xenopus embryo, we show that myocardin is sufficient to activate transcription of a wide range of cardiac and smooth muscle differentiation markers in non-muscle cell types. We also demonstrate that, for the myosin light chain 2 gene (MLC2), myocardin cooperates with the zinc-finger transcription factor Gata4 to activate expression. Inhibition of myocardin activity in Xenopus embryos using morpholino knockdown methods results in inhibition of cardiac development and the absence of expression of cardiac differentiation markers and severe disruption of cardiac morphological processes. We conclude that myocardin is an essential component of the regulatory pathway for myocardial differentiation.
authors.affiliation: Department of Cell Biology and Anatomy, University of Arizona Health Sciences Center, 1501 N. Campbell Avenue, PO Box 245044, Tucson, AZ 85724, USA.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Small
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Warkman
authors.forename: Da-Zhi
authors.initials: DZ
authors.lastname: Wang
authors.forename: Lillian B
authors.initials: LB
authors.lastname: Sutherland
authors.forename: Eric N
authors.initials: EN
authors.lastname: Olson
authors.forename: Paul A
authors.initials: PA
authors.lastname: Krieg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D024722:Cardiac Myosins / Q000378:metabolism; D002454:Cell Differentiation; D003001:Cloning, Molecular; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000378:metabolism; D050991:GATA4 Transcription Factor; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D005819:Genetic Markers; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000378:metabolism; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D018994:Myosin Light Chains / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000737:chemistry; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D020825:T-Box Domain Proteins / Q000378:metabolism; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics* / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D019076:Transgenes; D029867:Xenopus Proteins; D014982:Xenopus laevis; D000099251:Myocardin
chemical_list: D024722:Cardiac Myosins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D050991:GATA4 Transcription Factor; D005819:Genetic Markers; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; D018994:Myosin Light Chains; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense; D020825:T-Box Domain Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D029867:Xenopus Proteins; D000099251:Myocardin; C494751:GATA4 protein, Xenopus; C484469:Nkx2-5 protein, mouse; C103172:T-box transcription factor 5; C107184:myosin light chain 2