Six homeoproteins and a Iinc-RNA at the fast MYH locus lock fast myofiber terminal phenotype

Iori Sakakibara; Marc Santolini; Arnaud Ferry; Vincent Hakim; Pascal Maire

doi:10.1371/journal.pgen.1004386

Six homeoproteins and a Iinc-RNA at the fast MYH locus lock fast myofiber terminal phenotype

PLoS Genet. 2014 May 22;10(5):e1004386. doi: 10.1371/journal.pgen.1004386. eCollection 2014.

Authors

Iori Sakakibara¹, Marc Santolini², Arnaud Ferry³, Vincent Hakim², Pascal Maire¹

Affiliations

¹ INSERM U1016, Institut Cochin, Paris, France; CNRS UMR 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
² Laboratoire de Physique Statistique, CNRS, Université P. et M. Curie, Université D. Diderot, École Normale Supérieure, Paris, France.
³ 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.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cloning, Molecular
Enhancer Elements, Genetic
Extracellular Matrix Proteins / genetics
Gene Expression Regulation, Developmental
Homeodomain Proteins / genetics*
Homeodomain Proteins / metabolism
Mice, Knockout
Muscle Contraction / genetics*
Muscle, Skeletal / growth & development
Myosin Heavy Chains / genetics*
Protein-Lysine 6-Oxidase / genetics
RNA, Long Noncoding / genetics*

Substances

Extracellular Matrix Proteins
Homeodomain Proteins
RNA, Long Noncoding
Six1 protein, mouse
Lox protein, mouse
Protein-Lysine 6-Oxidase
Myosin Heavy Chains

Grants and funding

IS is supported by ANR, The Uehara Memorial Foundation and JSPS Postdoctoral Fellowships for Research Abroad. Financial support was provided by the Institut National de la Santé et la Recherche Médicale (INSERM), the “Association Française contre les Myopathies” (AFM), the Centre National de la Recherche Scientifique (CNRS), the Peps “Bio-Math-Info”, and the Agence Nationale pour la Recherche (ANR RPV09108KKA). We also acknowledge a contribution to the Institut Cochin animal care facility, made by the Région Ile de France. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.