Fig. 4.

The transcriptional activity of myocyte enhancer factor-2 (MEF2) factors is controlled by different repressors. MEF2 factors promote muscle growth during development and in the adult by regulating the expression of muscle-specific genes. MEF2 transcriptional activity is controlled by different repressors, including muscle-specific repressors like myogenic regulatory factor 4 (MRF4, coded by MYF6) and ubiquitous repressor as nuclear receptor co-repressor 1 (NCoR1) and class II histone deacetylases (HDACs), like HDAC4. Under normal conditions (upper panel) muscle size is maintained in the adult by a balance between these inhibitory factors and different stimulatory influences, including MEF2 post-translational changes, not depicted in the scheme. Loss of repressor activity (lower right panel), such as muscle-specific knockout of NCoR1 or muscle-specific knockdown of MRF4, lead to upregulation of MEF2 transcriptional activity and muscle hypertrophy. Increased repressor function (lower left panel), e.g. denervation-induced up-regulation and nuclear translocation of MRF4 and HDAC4, reduce MEF2 transcriptional activity and contribute to muscle atrophy.