MusTRD can regulate postnatal fiber-specific expression.
Human MusTRD1alpha1 was isolated as a result of its ability to bind a critical element within the Troponin I slow upstream enhancer (TnIslow USE) and was predicted to be a regulator of slow fiber-specific genes. To test this hypothesis in vivo, we generated transgenic mice expressing hMusTRD1alpha1 in skeletal muscle. Adult transgenic mice show a complete loss of slow fibers and a concomitant replacement by fast IIA fibers, resulting in postural muscle weakness. However, developmental analysis demonstrates that transgene expression has no impact on embryonic patterning of slow fibers but causes a gradual postnatal slow to fast fiber conversion. This conversion was underpinned by a demonstrable repression of many slow fiber-specific genes, whereas fast fiber-specific gene expression was either unchanged or enhanced. These data are consistent with our initial predictions for hMusTRD1alpha1 and suggest that slow fiber genes contain a specific common regulatory element that can be targeted by MusTRD proteins.
Muscle Development Unit, Children's Medical Research Institute, Wentworthville, NSW 2145, Australia.
Laura L
LL
Issa
Stephen J
SJ
Palmer
Kim L
KL
Guven
Nicole
N
Santucci
Vanessa R M
VR
Hodgson
Kata
K
Popovic
Josephine E
JE
Joya
Edna C
EC
Hardeman
D000818:Animals; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006614:Hindlimb / Q000166:cytology / Q000378:metabolism; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism*; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*
C405493:GTF2IRD1 protein, human; D009124:Muscle Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators