Overexpression of TEAD-1 in transgenic mouse striated muscles produces a slower skeletal muscle contractile phenotype.
TEA domain (TEAD) transcription factors serve important functional roles during embryonic development and in striated muscle gene expression. Our previous work has implicated a role for TEAD-1 in the fast-to-slow fiber-type transition in response to mechanical overload. To investigate whether TEAD-1 is a modulator of slow muscle gene expression in vivo, we developed transgenic mice expressing hemagglutinin (HA)-tagged TEAD-1 under the control of the muscle creatine kinase promoter. We show that striated muscle-restricted HA-TEAD-1 expression induced a transition toward a slow muscle contractile protein phenotype, slower shortening velocity (Vmax), and longer contraction and relaxation times in adult fast twitch extensor digitalis longus muscle. Notably, HA-TEAD-1 overexpression resulted in an unexpected activation of GSK-3alpha/beta and decreased nuclear beta-catenin and NFATc1/c3 protein. These effects could be reversed in vivo by mechanical overload, which decreased muscle creatine kinase-driven TEAD-1 transgene expression, and in cultured satellite cells by TEAD-1-specific small interfering RNA. These novel in vivo data support a role for TEAD-1 in modulating slow muscle gene expression.
Tsika
Richard W
RW
Department of Biochemistry, School of Medicine, University of Missouri, Columbia, Missouri 65211, USA. tsikar@missouri.edu
Schramm
Christine
C
Simmer
Gretchen
G
Fitzsimons
Daniel P
DP
Moss
Richard L
RL
Ji
Juan
J
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation; D007700:Kinetics; D051379:Mice; D008822:Mice, Transgenic; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism; D010641:Phenotype; D034741:RNA, Small Interfering / Q000378:metabolism; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology; D013314:Stress, Mechanical; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D019076:Transgenes
D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; D000091262:TEA Domain Transcription Factors; C083215:Tead1 protein, mouse; D014157:Transcription Factors