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

Nicolas Figeac, Abdalla D. Mohamed, Congshan Sun, Martin Schönfelder, David Matallanas, Amaya Garcia-Munoz, Edoardo Missiaglia, Elaina Collie-Duguid, Vanessa De Mello, Ajaybabu V. Pobbati, Johanna Pruller, Oihane Jaka, Stephen D. R. Harridge, Wanjin Hong, Janet Shipley, Neil Vargesson, Peter S. Zammit (Corresponding Author), Henning Wackerhage (Corresponding Author)

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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. Vgll3 is expressed at low levels in healthy muscle but levels increase during hypertrophy or regeneration, and in disease, VGLL3 is highly expressed in dystrophic muscle and alveolar rhabdomyosarcoma. Interaction proteomics revealed that VGLL3 binds TEAD1,3,4 in myoblasts and/or myotubes. However, there is no interaction with proteins of major regulatory systems such as the Hippo kinase cascade, unlike the TEAD cofactors YAP and TAZ. Vgll3 overexpression reduces the Hippo negative feedback loop, affecting expression of muscle-regulating genes including Myf5, Pitx2/3, Wnts and IGFBP. Vgll3 mainly represses gene expression, regulating similar genes to that of YAP1 and TAZ. SiRNA-mediated Vgll3 knockdown suppresses myoblast proliferation, while Vgll3 overexpression strongly promotes myogenic differentiation. Skeletal muscle is overtly normal in Vgll3-null mice though, presumably due to feedback signalling and/or redundancy. This work identifies Vgll3 as a transcriptional cofactor operating with the Hippo signal transduction network to control myogenesis.
Original languageEnglish
Article numberjcs225946
JournalJournal of Cell Science
Volume132
Early online date28 May 2019
DOIs
Publication statusPublished - 5 Jul 2019

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Muscle Development
Skeletal Muscle
Muscles
Myoblasts
Alveolar Rhabdomyosarcoma
Insulin-Like Growth Factor Binding Protein 3
Skeletal Muscle Fibers
Diptera
Proteomics
Hypertrophy
Genes
Regeneration
Signal Transduction
Proteins
Transcription Factors
Phosphotransferases
Gene Expression

Keywords

  • Vgll
  • Yap
  • Taz
  • Skeletal muscle
  • stem cells
  • WWTR1
  • TEAD
  • Stem cells
  • YAP
  • TAZ
  • VGLL3
  • TRANSCRIPTION FACTORS
  • PROTEIN
  • RHABDOMYOSARCOMA REVEALS
  • VESTIGIAL-LIKE
  • TISSUE
  • EFFECTOR
  • GENE-EXPRESSION
  • COFACTOR
  • BINDING

ASJC Scopus subject areas

  • Cell Biology

Cite this

Figeac, N., Mohamed, A. D., Sun, C., Schönfelder, M., Matallanas, D., Garcia-Munoz, A., ... Wackerhage, H. (2019). VGLL3 operates via TEAD1, TEAD3 and TEAD4 to influence myogenesis in skeletal muscle. Journal of Cell Science, 132, [jcs225946 ]. https://doi.org/10.1242/jcs.225946

VGLL3 operates via TEAD1, TEAD3 and TEAD4 to influence myogenesis in skeletal muscle. / Figeac, Nicolas; Mohamed, Abdalla D.; Sun, Congshan; Schönfelder, Martin; Matallanas, David; Garcia-Munoz, Amaya ; Missiaglia, Edoardo; Collie-Duguid, Elaina; De Mello, Vanessa; Pobbati, Ajaybabu V.; Pruller, Johanna; Jaka, Oihane; Harridge, Stephen D. R.; Hong, Wanjin; Shipley, Janet; Vargesson, Neil; Zammit, Peter S. (Corresponding Author); Wackerhage, Henning (Corresponding Author).

In: Journal of Cell Science, Vol. 132, jcs225946 , 05.07.2019.

Research output: Contribution to journalArticle

Figeac, N, Mohamed, AD, Sun, C, Schönfelder, M, Matallanas, D, Garcia-Munoz, A, Missiaglia, E, Collie-Duguid, E, De Mello, V, Pobbati, AV, Pruller, J, Jaka, O, Harridge, SDR, Hong, W, Shipley, J, Vargesson, N, Zammit, PS & Wackerhage, H 2019, 'VGLL3 operates via TEAD1, TEAD3 and TEAD4 to influence myogenesis in skeletal muscle', Journal of Cell Science, vol. 132, jcs225946 . https://doi.org/10.1242/jcs.225946
Figeac N, Mohamed AD, Sun C, Schönfelder M, Matallanas D, Garcia-Munoz A et al. VGLL3 operates via TEAD1, TEAD3 and TEAD4 to influence myogenesis in skeletal muscle. Journal of Cell Science. 2019 Jul 5;132. jcs225946 . https://doi.org/10.1242/jcs.225946
Figeac, Nicolas ; Mohamed, Abdalla D. ; Sun, Congshan ; Schönfelder, Martin ; Matallanas, David ; Garcia-Munoz, Amaya ; Missiaglia, Edoardo ; Collie-Duguid, Elaina ; De Mello, Vanessa ; Pobbati, Ajaybabu V. ; Pruller, Johanna ; Jaka, Oihane ; Harridge, Stephen D. R. ; Hong, Wanjin ; Shipley, Janet ; Vargesson, Neil ; Zammit, Peter S. ; Wackerhage, Henning. / VGLL3 operates via TEAD1, TEAD3 and TEAD4 to influence myogenesis in skeletal muscle. In: Journal of Cell Science. 2019 ; Vol. 132.
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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. Vgll3 is expressed at low levels in healthy muscle but levels increase during hypertrophy or regeneration, and in disease, VGLL3 is highly expressed in dystrophic muscle and alveolar rhabdomyosarcoma. Interaction proteomics revealed that VGLL3 binds TEAD1,3,4 in myoblasts and/or myotubes. However, there is no interaction with proteins of major regulatory systems such as the Hippo kinase cascade, unlike the TEAD cofactors YAP and TAZ. Vgll3 overexpression reduces the Hippo negative feedback loop, affecting expression of muscle-regulating genes including Myf5, Pitx2/3, Wnts and IGFBP. Vgll3 mainly represses gene expression, regulating similar genes to that of YAP1 and TAZ. SiRNA-mediated Vgll3 knockdown suppresses myoblast proliferation, while Vgll3 overexpression strongly promotes myogenic differentiation. Skeletal muscle is overtly normal in Vgll3-null mice though, presumably due to feedback signalling and/or redundancy. This work identifies Vgll3 as a transcriptional cofactor operating with the Hippo signal transduction network to control myogenesis.",
keywords = "Vgll, Yap, Taz, Skeletal muscle, stem cells, WWTR1, TEAD, Stem cells, YAP, TAZ, VGLL3, TRANSCRIPTION FACTORS, PROTEIN, RHABDOMYOSARCOMA REVEALS, VESTIGIAL-LIKE, TISSUE, EFFECTOR, GENE-EXPRESSION, COFACTOR, BINDING",
author = "Nicolas Figeac and Mohamed, {Abdalla D.} and Congshan Sun and Martin Sch{\"o}nfelder and David Matallanas and Amaya Garcia-Munoz and Edoardo Missiaglia and Elaina Collie-Duguid and {De Mello}, Vanessa and Pobbati, {Ajaybabu V.} and Johanna Pruller and Oihane Jaka and Harridge, {Stephen D. R.} and Wanjin Hong and Janet Shipley and Neil Vargesson and Zammit, {Peter S.} and Henning Wackerhage",
note = "Acknowledgements We are grateful to the MRC Harwell facility for generating and providing Vgll3-/- mice and Annett Riermeier for mouse phenotyping. We thank Dr. Vincent Mouly (Institute Myology, Paris, France) for human immortalised myoblasts. Funding NF was initially funded by the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement number 262948–2 (BIODESIGN), and then supported by the KHP R&D Challenge Fund (R151006) and the Medical Research Council (MR/P023215/1). AM was funded initially by Sarcoma UK (grant number: SUK09.2015) and then supported by funding from Postdoctoral Fellowship Program (Helmholtz Center, Munich, Germany). CS was funded by MRC grant G11001931 to HW and PSZ, and then BIODESIGN. JP is in receipt of a Wellcome Trust PhD Studentship (WT - 203949/Z/16/Z). The Zammit laboratory was additionally supported by Association Francaise contre les Myopathies (17865). This research is also supported by the Agency for Science, Technology, and Research (A*STAR), Singapore.",
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T1 - VGLL3 operates via TEAD1, TEAD3 and TEAD4 to influence myogenesis in skeletal muscle

AU - Figeac, Nicolas

AU - Mohamed, Abdalla D.

AU - Sun, Congshan

AU - Schönfelder, Martin

AU - Matallanas, David

AU - Garcia-Munoz, Amaya

AU - Missiaglia, Edoardo

AU - Collie-Duguid, Elaina

AU - De Mello, Vanessa

AU - Pobbati, Ajaybabu V.

AU - Pruller, Johanna

AU - Jaka, Oihane

AU - Harridge, Stephen D. R.

AU - Hong, Wanjin

AU - Shipley, Janet

AU - Vargesson, Neil

AU - Zammit, Peter S.

AU - Wackerhage, Henning

N1 - Acknowledgements We are grateful to the MRC Harwell facility for generating and providing Vgll3-/- mice and Annett Riermeier for mouse phenotyping. We thank Dr. Vincent Mouly (Institute Myology, Paris, France) for human immortalised myoblasts. Funding NF was initially funded by the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement number 262948–2 (BIODESIGN), and then supported by the KHP R&D Challenge Fund (R151006) and the Medical Research Council (MR/P023215/1). AM was funded initially by Sarcoma UK (grant number: SUK09.2015) and then supported by funding from Postdoctoral Fellowship Program (Helmholtz Center, Munich, Germany). CS was funded by MRC grant G11001931 to HW and PSZ, and then BIODESIGN. JP is in receipt of a Wellcome Trust PhD Studentship (WT - 203949/Z/16/Z). The Zammit laboratory was additionally supported by Association Francaise contre les Myopathies (17865). This research is also supported by the Agency for Science, Technology, and Research (A*STAR), Singapore.

PY - 2019/7/5

Y1 - 2019/7/5

N2 - 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. Vgll3 is expressed at low levels in healthy muscle but levels increase during hypertrophy or regeneration, and in disease, VGLL3 is highly expressed in dystrophic muscle and alveolar rhabdomyosarcoma. Interaction proteomics revealed that VGLL3 binds TEAD1,3,4 in myoblasts and/or myotubes. However, there is no interaction with proteins of major regulatory systems such as the Hippo kinase cascade, unlike the TEAD cofactors YAP and TAZ. Vgll3 overexpression reduces the Hippo negative feedback loop, affecting expression of muscle-regulating genes including Myf5, Pitx2/3, Wnts and IGFBP. Vgll3 mainly represses gene expression, regulating similar genes to that of YAP1 and TAZ. SiRNA-mediated Vgll3 knockdown suppresses myoblast proliferation, while Vgll3 overexpression strongly promotes myogenic differentiation. Skeletal muscle is overtly normal in Vgll3-null mice though, presumably due to feedback signalling and/or redundancy. This work identifies Vgll3 as a transcriptional cofactor operating with the Hippo signal transduction network to control myogenesis.

AB - 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. Vgll3 is expressed at low levels in healthy muscle but levels increase during hypertrophy or regeneration, and in disease, VGLL3 is highly expressed in dystrophic muscle and alveolar rhabdomyosarcoma. Interaction proteomics revealed that VGLL3 binds TEAD1,3,4 in myoblasts and/or myotubes. However, there is no interaction with proteins of major regulatory systems such as the Hippo kinase cascade, unlike the TEAD cofactors YAP and TAZ. Vgll3 overexpression reduces the Hippo negative feedback loop, affecting expression of muscle-regulating genes including Myf5, Pitx2/3, Wnts and IGFBP. Vgll3 mainly represses gene expression, regulating similar genes to that of YAP1 and TAZ. SiRNA-mediated Vgll3 knockdown suppresses myoblast proliferation, while Vgll3 overexpression strongly promotes myogenic differentiation. Skeletal muscle is overtly normal in Vgll3-null mice though, presumably due to feedback signalling and/or redundancy. This work identifies Vgll3 as a transcriptional cofactor operating with the Hippo signal transduction network to control myogenesis.

KW - Vgll

KW - Yap

KW - Taz

KW - Skeletal muscle

KW - stem cells

KW - WWTR1

KW - TEAD

KW - Stem cells

KW - YAP

KW - TAZ

KW - VGLL3

KW - TRANSCRIPTION FACTORS

KW - PROTEIN

KW - RHABDOMYOSARCOMA REVEALS

KW - VESTIGIAL-LIKE

KW - TISSUE

KW - EFFECTOR

KW - GENE-EXPRESSION

KW - COFACTOR

KW - BINDING

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U2 - 10.1242/jcs.225946

DO - 10.1242/jcs.225946

M3 - Article

VL - 132

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

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