MusTRD can regulate postnatal fiber-specific expression |
| |
Authors: | Issa Laura L Palmer Stephen J Guven Kim L Santucci Nicole Hodgson Vanessa R M Popovic Kata Joya Josephine E Hardeman Edna C |
| |
Institution: | Muscle Development Unit, Children's Medical Research Institute, Wentworthville, NSW 2145, Australia. |
| |
Abstract: | 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. |
| |
Keywords: | |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|