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  MRF4 negatively regulates adult skeletal muscle growth by repressing MEF2 activity

Moretti, I., Ciciliot, S., Dyar, K. A., Abraham, R., Murgia, M., Agatea, L., et al. (2016). MRF4 negatively regulates adult skeletal muscle growth by repressing MEF2 activity. Nature Communications, 7: 12397. doi:10.1038/ncomms12397.

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 Creators:
Moretti, Irene1, Author
Ciciliot, Stefano1, Author
Dyar, Kenneth A.1, Author
Abraham, Reimar1, Author
Murgia, Marta2, Author           
Agatea, Lisa1, Author
Akimoto, Takayuki1, Author
Bicciato, Silvio1, Author
Forcato, Mattia1, Author
Pierre, Philippe1, Author
Uhlenhaut, N. Henriette1, Author
Rigby, Peter W. J.1, Author
Carvajal, Jaime J.1, Author
Blaauw, Bert1, Author
Calabria, Elisa1, Author
Schiaffino, Stefano1, Author
Affiliations:
1external, ou_persistent22              
2Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159              

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Free keywords: MYOSIN HEAVY-CHAIN; TRANSCRIPTION FACTORS; GENE-EXPRESSION; HEART-FAILURE; MYOGENIN; ACTIVATION; HDAC4; DIFFERENTIATION; REGENERATION; DYSFUNCTIONScience & Technology - Other Topics;
 Abstract: The myogenic regulatory factor MRF4 is highly expressed in adult skeletal muscle but its function is unknown. Here we show that Mrf4 knockdown in adult muscle induces hypertrophy and prevents denervation-induced atrophy. This effect is accompanied by increased protein synthesis and widespread activation of muscle-specific genes, many of which are targets of MEF2 transcription factors. MEF2-dependent genes represent the top-ranking gene set enriched after Mrf4 RNAi and a MEF2 reporter is inhibited by co-transfected MRF4 and activated by Mrf4 RNAi. The Mrf4 RNAi-dependent increase in fibre size is prevented by dominant negative MEF2, while constitutively active MEF2 is able to induce myofibre hypertrophy. The nuclear localization of the MEF2 corepressor HDAC4 is impaired by Mrf4 knockdown, suggesting that MRF4 acts by stabilizing a repressor complex that controls MEF2 activity. These findings open new perspectives in the search for therapeutic targets to prevent muscle wasting, in particular sarcopenia and cachexia.

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Language(s): eng - English
 Dates: 2016-05-242016-06-282016-08-03
 Publication Status: Published online
 Pages: 12
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000380862800001
DOI: 10.1038/ncomms12397
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Title: Nature Communications
  Abbreviation : Nat. Commun.
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 7 Sequence Number: 12397 Start / End Page: - Identifier: ISSN: 2041-1723
CoNE: https://pure.mpg.de/cone/journals/resource/2041-1723