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The LIM domain protein nTRIP6 acts as a co-repressor for the transcription factor MEF2C in myoblasts

Kemler, Denise 1; Dahley, Oliver 1; Roßwag, Sven 1; Litfin, Margarethe 1; Kassel, Olivier ORCID iD icon 1
1 Institut für Toxikologie und Genetik (ITG), Karlsruher Institut für Technologie (KIT)

Abstract:

The transcription factor Myocyte enhancer factor 2C (MEF2C) plays a key role in the late differentiation of skeletal muscle progenitor cells, the so-called myoblasts. During myoblast differentiation, both MEF2C expression and transcriptional activity are regulated. We have reported that nTRIP6, the nuclear isoform of the focal adhesion LIM domain protein TRIP6, acts as an adaptor transcriptional co-activator for several transcription factors. It interacts with the promoter-bound transcription factors and consequently mediates the recruitment of other co-activators. Based on a described interaction between MEF2C and TRIP6 in a yeast-two-hybrid screen, we hypothesised a co-regulatory function of nTRIP6 for MEF2C. In proliferating myoblasts, nTRIP6 interacted with MEF2C and was recruited together with MEF2C to the MEF2-binding regions of the MEF2C target genes Myom2, Mb, Tnni2 and Des. Silencing nTRIP6 or preventing its interaction with MEF2C increased MEF2C transcriptional activity and increased the expression of these MEF2C target genes. Thus, nTRIP6 acts as a co-repressor for MEF2C. Mechanistically, nTRIP6 mediated the recruitment of the class IIa histone deacetylase HDAC5 to the MEF2C-bound promoters. ... mehr


Volltext §
DOI: 10.5445/IR/1000055683
Originalveröffentlichung
DOI: 10.1038/srep27746
Scopus
Zitationen: 7
Web of Science
Zitationen: 8
Dimensions
Zitationen: 9
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Toxikologie und Genetik (ITG)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2016
Sprache Englisch
Identifikator ISSN: 2045-2322
urn:nbn:de:swb:90-556830
KITopen-ID: 1000055683
HGF-Programm 47.01.01 (POF III, LK 01) Biol.Netzwerke u.Synth.Regulat. ITG+ITC
Erschienen in Scientific reports
Verlag Nature Research
Band 6
Seiten Art. Nr. 27746
Bemerkung zur Veröffentlichung Gefördert durch den KIT-Publikationsfonds
Vorab online veröffentlicht am 13.06.2016
Schlagwörter Differentiation; Gene regulation Transcription
Nachgewiesen in Web of Science
Dimensions
Scopus
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