RE1-silencing transcription factor (REST) and its possible role in skeletal muscle

RE-silencing transcription factor (REST) is a DNA binding protein able to assemble a repressor complex on Repressor Element 1 (RE-1) sequences, which are present near more than 1000 genes in the human genome. The N-terminus of REST binds mSin3A/B co-repressor and the histone-deacetylases HDAC1/2 proteins, whilst the C-terminus binds the Co-REST corepressor. REST is considered to be a repressor of neuronal genes in nonneuronal tissues, however it is now known that it has additional functions, ranging from pro-oncogenic and tumor suppressor activities, involvement in ageing and neurodegenerative diseases. REST has also been shown to play a role in cardiomyocyte differentiation and is expressed in skeletal muscle, although its function in these cells in unknown. On this note, the transcriptional network which drives the myogenic differentiation and regeneration programs is accompanied by epigenetic modifications which involve HDACs and, importantly REST is able to form a transcriptional repression complex with HDACs. Therefore we decided to further investigate the role of REST and HDACs in striated muscles. We generated a conditional knockout mouse model using the LoxP-CRE technology, with CRE expressed by the muscle-specific MyoD promoter. Our results show that upon REST deletion in skeletal muscle, physical performance seems to improve and the diameter of muscle fibers is reduced, suggesting the presence of a muscle regeneration process. Furthermore, the amount of satellite cells does not vary from wild-type condition. Altogether, our hypothesis is that REST may form a transcriptional complex able to regulate muscle differentiation.