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dc.contributor.authorFigeac, N
dc.contributor.authorMohamed, AD
dc.contributor.authorSun, C
dc.contributor.authorSchönfelder, M
dc.contributor.authorMatallanas, D
dc.contributor.authorGarcia-Munoz, A
dc.contributor.authorMissiaglia, E
dc.contributor.authorCollie-Duguid, E
dc.contributor.authorDe Mello, V
dc.contributor.authorPobbati, AV
dc.contributor.authorPruller, J
dc.contributor.authorJaka, O
dc.contributor.authorHarridge, SDR
dc.contributor.authorHong, W
dc.contributor.authorShipley, J
dc.contributor.authorVargesson, N
dc.contributor.authorZammit, PS
dc.contributor.authorWackerhage, H
dc.date.accessioned2020-06-03T13:41:38Z
dc.date.issued2019-07-05
dc.identifier.citationJournal of cell science, 2019, 132 (13)
dc.identifier.issn0021-9533
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3691
dc.identifier.eissn1477-9137
dc.identifier.doi10.1242/jcs.225946
dc.description.abstractVGLL 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.
dc.formatElectronic
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectMuscle, Skeletal
dc.subjectMyoblasts
dc.subjectAnimals
dc.subjectMice, Knockout
dc.subjectHumans
dc.subjectNeoplasms
dc.subjectMuscle Proteins
dc.subjectDNA-Binding Proteins
dc.subjectNuclear Proteins
dc.subjectTranscription Factors
dc.subjectCell Differentiation
dc.subjectCell Proliferation
dc.subjectGene Expression Regulation
dc.subjectProtein Binding
dc.subjectMuscle Development
dc.subjectMuscle Fibers, Skeletal
dc.subjectHEK293 Cells
dc.subjectTranscriptome
dc.titleVGLL3 operates via TEAD1, TEAD3 and TEAD4 to influence myogenesis in skeletal muscle.
dc.typeJournal Article
dcterms.dateAccepted2019-05-03
rioxxterms.versionofrecord10.1242/jcs.225946
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2019-07-05
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfJournal of cell science
pubs.issue13
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Sarcoma Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Sarcoma Molecular Pathology
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Sarcoma Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Sarcoma Molecular Pathology
pubs.publication-statusPublished
pubs.volume132
pubs.embargo.termsNot known
icr.researchteamSarcoma Molecular Pathologyen_US
dc.contributor.icrauthorShipley, Janeten


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