Six homeoproteins and a Iinc-RNA at the fast MYH locus lock fast myofiber terminal phenotype.
Thousands of long intergenic non-coding RNAs (lincRNAs) are encoded by the mammalian genome. However, the function of most of these lincRNAs has not been identified in vivo. Here, we demonstrate a role for a novel lincRNA, linc-MYH, in adult fast-type myofiber specialization. Fast myosin heavy chain (MYH) genes and linc-MYH share a common enhancer, located in the fast MYH gene locus and regulated by Six1 homeoproteins. linc-MYH in nuclei of fast-type myofibers prevents slow-type and enhances fast-type gene expression. Functional fast-sarcomeric unit formation is achieved by the coordinate expression of fast MYHs and linc-MYH, under the control of a common Six-bound enhancer.
INSERM U1016, Institut Cochin, Paris, France; CNRS UMR 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Iori
I
Sakakibara
Laboratoire de Physique Statistique, CNRS, Université P. et M. Curie, Université D. Diderot, École Normale Supérieure, Paris, France.
Marc
M
Santolini
CNRS UMR 8104, Paris, France; Université Pierre et Marie Curie-Paris 6, Sorbonne Universités, UMR S794, INSERM U974, CNRS UMR7215, Institut de Myologie, Paris, France.
Arnaud
A
Ferry
Laboratoire de Physique Statistique, CNRS, Université P. et M. Curie, Université D. Diderot, École Normale Supérieure, Paris, France.
Vincent
V
Hakim
INSERM U1016, Institut Cochin, Paris, France; CNRS UMR 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Pascal
P
Maire
D000818:Animals; D003001:Cloning, Molecular; D004742:Enhancer Elements, Genetic; D016326:Extracellular Matrix Proteins / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000235:genetics*; D018482:Muscle, Skeletal / Q000254:growth & development; D018995:Myosin Heavy Chains / Q000235:genetics*; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics*
D016326:Extracellular Matrix Proteins; D018398:Homeodomain Proteins; D062085:RNA, Long Noncoding; C490947:Six1 protein, mouse; C077112:Lox protein, mouse; D008249:Protein-Lysine 6-Oxidase; D018995:Myosin Heavy Chains