VGLL3 operates via TEAD1, TEAD3 and TEAD4 to influence myogenesis in skeletal muscle.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_65F77A5F1F41
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
VGLL3 operates via TEAD1, TEAD3 and TEAD4 to influence myogenesis in skeletal muscle.
Journal
Journal of cell science
Author(s)
Figeac N., Mohamed A.D., Sun C., Schönfelder M., Matallanas D., Garcia-Munoz A., Missiaglia E., Collie-Duguid E., De Mello V., Pobbati A.V., Pruller J., Jaka O., Harridge SDR, Hong W., Shipley J., Vargesson N., Zammit P.S., Wackerhage H.
ISSN
1477-9137 (Electronic)
ISSN-L
0021-9533
Publication state
Published
Issued date
05/07/2019
Peer-reviewed
Oui
Volume
132
Number
13
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
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.
Keywords
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, Skeletal muscle, Stem cells, TAZ, TEAD, VGLL3, WWTR1, YAP
Pubmed
Web of science
Open Access
Yes
Create date
05/06/2019 9:47
Last modification date
25/07/2020 6:19
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