The LIM domain protein nTRIP6 acts as a co-repressor for the transcription factor MEF2C in myoblasts.
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. In conclusion, our results unravel a transcriptional co-repressor function for nTRIP6. This adaptor co-regulator can thus exert either co-activator or co-repressor functions, depending on the transcription factor it interacts with.
Karlsruhe Institute of Technology (KIT), Institute of Toxicology and Genetics, Karlsruhe, Germany.
Denise
D
Kemler
Karlsruhe Institute of Technology (KIT), Institute of Toxicology and Genetics, Karlsruhe, Germany.
Oliver
O
Dahley
Karlsruhe Institute of Technology (KIT), Institute of Toxicology and Genetics, Karlsruhe, Germany.
Sven
S
Roßwag
Karlsruhe Institute of Technology (KIT), Institute of Toxicology and Genetics, Karlsruhe, Germany.
Margarethe
M
Litfin
Karlsruhe Institute of Technology (KIT), Institute of Toxicology and Genetics, Karlsruhe, Germany.
Olivier
O
Kassel
D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D064211:Connectin / Q000235:genetics; D060588:LIM Domain Proteins / Q000737:chemistry* / Q000378:metabolism*; D064326:MEF2 Transcription Factors / Q000378:metabolism; D051379:Mice; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D000072417:Protein Domains; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism*; D019210:Troponin I / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D064211:Connectin; D060588:LIM Domain Proteins; D064326:MEF2 Transcription Factors; C578041:Mef2c protein, mouse; C577288:Myom2 protein, mouse; D014157:Transcription Factors; C000614137:Trip6 protein, mouse; D019210:Troponin I