VGLL3 operates via TEAD1, TEAD3 and TEAD4 to influence myogenesis in skeletal muscle
| Autor: | Figeac, Nicolas, Mohamed, Abdalla, Sun, Congshan, Schonfelder, Martin, Matallanas, David, Garcia-Munoz, Amaya, Missiaglia, Edoardo, Collie-Duguid, Elaina, De Mello, Vanessa, Pobbati, Ajaybabu, Prueller, Johanna, Jaka Irizar, Oihane, Harridge, Stephen David Royston, Hong, Wanjin, Shipley, Janet, Vargesson, Neil, Zammit, Peter Steven, Wackerhage, Henning |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
TAZ
Muscle Fibers Skeletal Muscle Proteins Skeletal muscle WWTR1 Stem cells Muscle Development Animals Cell Differentiation/genetics Cell Proliferation/genetics DNA-Binding Proteins/metabolism Gene Expression Regulation HEK293 Cells Humans Mice Knockout Muscle Development/genetics Muscle Fibers Skeletal/metabolism Muscle Proteins/metabolism Muscle Skeletal/metabolism Myoblasts/metabolism Neoplasms/metabolism Nuclear Proteins/metabolism Protein Binding Transcription Factors/metabolism Transcriptome/genetics TEAD VGLL3 YAP Myoblasts Neoplasms Vgll3 Tead Yap Taz Wwtr1 Skeletal Muscle Stem Cells Muscle Skeletal Cell Proliferation Nuclear Proteins TEA Domain Transcription Factors Cell Differentiation DNA-Binding Proteins Transcriptome Transcription Factors Research Article |
| Zdroj: | J. Cell Sci. 132:jcs225946 (2019) Journal of Cell Science Journal of cell science, vol. 132, no. 13 Figeac, N, Mohamed, A, Sun, C, Schonfelder, M, Matallanas, D, Garcia-Munoz, A, Missiaglia, E, Collie-Duguid, E, De Mello, V, Pobbati, A, Prueller, J, Jaka Irizar, O, Harridge, S D R, Hong, W, Shipley, J, Vargesson, N, Zammit, P S & Wackerhage, H 2019, ' Vgll3 operates via Tead1, Tead3 and Tead4 to influence myogenesis in skeletal muscle ', Journal of Cell Science, vol. 132, no. 13, 225946 . https://doi.org/10.1242/jcs.225946 |
| DOI: | 10.1242/jcs.225946 |
| Popis: | VGLL proteins are transcriptional co-factors that bind TEAD family transcription factors to regulate events ranging from wing development in fly, to muscle fibre composition and immune function in mice. Here, we characterise Vgll3 in skeletal muscle. We found that mouse Vgll3 was expressed at low levels in healthy muscle but that its levels increased during hypertrophy or regeneration; in humans, VGLL3 was highly expressed in tissues from patients with various muscle diseases, such as in dystrophic muscle and alveolar rhabdomyosarcoma. Interaction proteomics revealed that VGLL3 bound TEAD1, TEAD3 and TEAD4 in myoblasts and/or myotubes. However, there was no interaction with proteins from major regulatory systems such as the Hippo kinase cascade, unlike what is found for the TEAD co-factors YAP (encoded by YAP1) and TAZ (encoded by WWTR1). Vgll3 overexpression reduced the activity of the Hippo negative-feedback loop, affecting expression of muscle-regulating genes including Myf5, Pitx2 and Pitx3, and genes encoding certain Wnts and IGFBPs. VGLL3 mainly repressed gene expression, regulating similar genes to those regulated by YAP and TAZ. siRNA-mediated Vgll3 knockdown suppressed myoblast proliferation, whereas Vgll3 overexpression strongly promoted myogenic differentiation. However, skeletal muscle was overtly normal in Vgll3-null mice, presumably due to feedback signalling and/or redundancy. This work identifies VGLL3 as a transcriptional co-factor operating with the Hippo signal transduction network to control myogenesis. Summary: VGLL3 interacts with TEAD transcription factors to direct expression of crucial muscle regulatory genes and contribute to the control of skeletal myogenesis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|