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Publication : Myod1 and GR coordinate myofiber-specific transcriptional enhancers.

First Author  Rovito D Year  2021
Journal  Nucleic Acids Res Volume  49
Issue  8 Pages  4472-4492
PubMed ID  33836079 Mgi Jnum  J:316354
Mgi Id  MGI:6710062 Doi  10.1093/nar/gkab226
Citation  Rovito D, et al. (2021) Myod1 and GR coordinate myofiber-specific transcriptional enhancers. Nucleic Acids Res 49(8):4472-4492
abstractText  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.
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