@article { , title = {c-Myc inhibits myoblast differentiation and promotes myoblast proliferation and muscle fibre hypertrophy by regulating the expression of its target genes, miRNAs and lincRNAs}, abstract = {© 2018, ADMC Associazione Differenziamento e Morte Cellulare. The transcription factor c-Myc is an important regulator of cellular proliferation, differentiation and embryogenesis. While c-Myc can inhibit myoblast differentiation, the underlying mechanisms remain poorly understood. Here, we found that c-Myc does not only inhibits myoblast differentiation but also promotes myoblast proliferation and muscle fibre hypertrophy. By performing chromatin immunoprecipitation and high-throughput sequencing (ChIP-seq), we identified the genome-wide binding profile of c-Myc in skeletal muscle cells. c-Myc achieves its regulatory effects on myoblast proliferation and differentiation by targeting the cell cycle pathway. Additionally, c-Myc can regulate cell cycle genes by controlling miRNA expression of which dozens of miRNAs can also be regulated directly by c-Myc. Among these c-Myc-associated miRNAs (CAMs), the roles played by c-Myc-induced miRNAs in skeletal muscle cells are similar to those played by c-Myc, whereas c-Myc-repressed miRNAs play roles that are opposite to those played by c-Myc. The cell cycle, ERK–MAPK and Akt-mediated pathways are potential target pathways of the CAMs during myoblast differentiation. Interestingly, we identified four CAMs that can directly bind to the c-Myc 3' UTR and inhibit c-Myc expression, suggesting that a negative feedback loop exists between c-Myc and its target miRNAs during myoblast differentiation. c-Myc also potentially regulates many long intergenic noncoding RNAs (lincRNAs). Linc-2949 and linc-1369 are directly regulated by c-Myc, and both lincRNAs are involved in the regulation of myoblast proliferation and differentiation by competing for the binding of muscle differentiation-related miRNAs. Our findings do not only provide a genome-wide overview of the role the c-Myc plays in skeletal muscle cells but also uncover the mechanism of how c-Myc and its target genes regulate myoblast proliferation and differentiation, and muscle fibre hypertrophy.}, doi = {10.1038/s41418-018-0129-0}, eissn = {1476-5403}, issn = {1350-9047}, issue = {3}, journal = {Cell Death and Differentiation}, note = {Deposited without AAM. Make discoverable without AAM KH 22.01.2021}, pages = {426-442}, publicationstatus = {Published}, publisher = {Nature Publishing Group}, url = {https://nottingham-repository.worktribe.com/output/3119214}, volume = {26}, year = {2019}, author = {Luo, Wen and Chen, Jiahui and Li, Limin and Ren, Xueyi and Cheng, Tian and Lu, Shiyi and Lawal, Raman Akinyanju and Nie, Qinghua and Zhang, Xiquan and Hanotte, Olivier} }