Skeletal muscle is a dynamic tissue the size of which can be remodeled through the concerted actions of various cues. Here, we investigated the skeletal muscle transcriptional program and identified key tissue-specific regulatory genetic elements. Our results show that Myod1 is bound to numerous skeletal muscle enhancers in collaboration with the glucocorticoid receptor (GR) to control gene expression. Remarkably, transcriptional activation controlled by these factors occurs through direct contacts with the promoter region of target genes, via the CpG-bound transcription factor Nrf1, and the formation of Ctcf-anchored chromatin loops, in a myofiber-specific manner. Moreover, we demonstrate that GR negatively controls muscle mass and strength in mice by down-regulating anabolic pathways. Taken together, our data establish Myod1, GR and Nrf1 as key players of muscle-specific enhancer-promoter communication that orchestrate myofiber size regulation.

Gonad-related factors promote muscle performance gain during postnatal development in male and female mice http://researchonline.ljmu.ac.uk/7509/ Article LJMU has developed LJMU Research Online for users to access the research output of the University more effectively. Copyright © and Moral Rights for the papers on this site are retained by the individual authors and/or other copyright owners. Users may download and/or print one copy of any article(s) in LJMU Research Online to facilitate their private study or for non-commercial research. You may not engage in further distribution of the material or use it for any profit-making activities or any commercial gain.The version presented here may differ from the published version or from the version of the record. Please see the repository URL above for details on accessing the published version and note that access may require a subscription. Abstract 26 27In order to better define the role of male and female gonad-related factors (MGRF,28 presumably testosterone, and FGRF, presumably estradiol, respectively) on mouse hindlimb 29 skeletal muscle contractile performance/function gain during postnatal development, we 30 analysed the effect of castration initiated before puberty in male and female mice. We found 31 that muscle absolute and specific (normalized to muscle weight) maximal forces 32 weresdecreased in 6-month old male and female castrated mice, as compared to age-and 33 sex-matched intact mice, without alteration in neuromuscular transmission. Moreover, 34 castration decreased absolute and specific maximal powers, another important aspect of 35 muscle performance, in 6-month old males, but not in females. Absolute maximal force was 36 similarly reduced by castration in 3-month old muscle fibre androgen receptor (AR) -37 deficient and wild-type male mice, indicating that the effect of MGRF was muscle fibre AR 38 independent. Castration reduced the muscle weight gain in 3-month mice of both sexes and 39 in 6-month females but not in males. We also found that bone morphogenetic protein 40 signaling through Smad1/5/9 was not altered by castration in atrophic muscle of 3-month old 41 mice of both sexes. Moreover, castration decreased the sexual dimorphism regarding muscle 42performance. Together these results demonstrated that in the long-term MGRF and FGRF 43 promote muscle performance gain in mice during postnatal development, independently of 44 muscle growth in males, largely via improving muscle contractile quality (force and power 45 normalized) and that MGFR and FGRF also contribute to sexual dimorphism. However, the 46 mechanisms underlying MGFR and FGRF actions remain to be determined.