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

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Title: VGLL3 operates via TEAD1, TEAD3 and TEAD4 to influence myogenesis in skeletal muscle
Authors: Figeac, NicolasMohamed, Abdalla D.Sun, CongshanMatallanas, DavidGarcia Munoz, Amayaet al.
Permanent link: http://hdl.handle.net/10197/11882
Date: 5-Jul-2019
Online since: 2021-01-25T13:11:37Z
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.
Funding Details: European Commission - Seventh Framework Programme (FP7)
Wellcome Trust
Funding Details: King's Health Partners R&D Challenge Fund
Medical Research Council
Sarcoma UK
Postdoctoral Fellowship Program (Helmholtz Center, Munich, Germany)
MRC
Biotechnology and Biological Sciences Research Council
Association Fran├žaise contre les Myopathies
Agency for Science, Technology and Research (A*STAR), Singapore
Type of material: Journal Article
Publisher: Company of Biologists
Journal: Journal of Cell Science
Volume: 132
Issue: 13
Copyright (published version): 2019 The Company of Biologists
Keywords: GeneticsBiotechnologyRare diseasesStem cellsSkeletal muscleVGLL3TEADYAPTAZWWTR1
DOI: 10.1242/jcs.225946
Language: en
Status of Item: Peer reviewed
ISSN: 0021-9533
This item is made available under a Creative Commons License: https://creativecommons.org/licenses/by/3.0/ie/
Appears in Collections:SBI Research Collection
Medicine Research Collection

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