title: miR-98 delays skeletal muscle differentiation by down-regulating E2F5.
abstract: A genome-wide screen had previously shown that knocking down miR-98 and let-7g, two miRNAs of the let-7 family, leads to a dramatic increase in terminal myogenic differentiation. In the present paper, we report that a transcriptomic analysis of human myoblasts, where miR-98 was knocked down, revealed that approximately 240 genes were sensitive to miR-98 depletion. Among these potential targets of miR-98, we identified the transcriptional repressor E2F5 and showed that it is a direct target of miR-98. Knocking down simultaneously E2F5 and miR-98 almost fully restored normal differentiation, indicating that E2F5 is involved in the regulation of skeletal muscle differentiation. We subsequently show that E2F5 can bind to the promoters of two inhibitors of terminal muscle differentiation, ID1 (inhibitor of DNA binding 1) and HMOX1 (heme oxygenase 1), which decreases their expression in skeletal myoblasts. We conclude that miR-98 regulates muscle differentiation by altering the expression of the transcription factor E2F5 and, in turn, of multiple E2F5 targets.
authors.affiliation: *CNRS FRE 3377, CEA Saclay, F-91191 Gif-sur-Yvette, France.
authors.forename: Jeremie
authors.initials: J
authors.lastname: Kropp
authors.affiliation: *CNRS FRE 3377, CEA Saclay, F-91191 Gif-sur-Yvette, France.
authors.forename: Cindy
authors.initials: C
authors.lastname: Degerny
authors.affiliation: *CNRS FRE 3377, CEA Saclay, F-91191 Gif-sur-Yvette, France.
authors.forename: Nadezda
authors.initials: N
authors.lastname: Morozova
authors.affiliation: §Université Paris Diderot, Sorbonne Paris Cité, Laboratoire Epigénétique et Destin Cellulaire, UMR7216, Centre National de la Recherche Scientifique CNRS, 35 rue Hélène Brion, 75013 Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Pontis
authors.affiliation: *CNRS FRE 3377, CEA Saclay, F-91191 Gif-sur-Yvette, France.
authors.forename: Annick
authors.initials: A
authors.lastname: Harel-Bellan
authors.affiliation: *CNRS FRE 3377, CEA Saclay, F-91191 Gif-sur-Yvette, France.
authors.forename: Anna
authors.initials: A
authors.lastname: Polesskaya
mesh_terms: D002454:Cell Differentiation / Q000235:genetics*; D050700:E2F5 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D024510:Muscle Development / Q000235:genetics; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome
chemical_list: D050700:E2F5 Transcription Factor; C092558:E2F5 protein, human; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; C546084:MIRN98 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1