title: myomiR-dependent switching of BAF60 variant incorporation into Brg1 chromatin remodeling complexes during embryo myogenesis.
abstract: Myogenesis involves the stable commitment of progenitor cells followed by the execution of myogenic differentiation, processes that are coordinated by myogenic regulatory factors, microRNAs and BAF chromatin remodeling complexes. BAF60a, BAF60b and BAF60c are structural subunits of the BAF complex that bind to the core ATPase Brg1 to provide functional specificity. BAF60c is essential for myogenesis; however, the mechanisms regulating the subunit composition of BAF/Brg1 complexes, in particular the incorporation of different BAF60 variants, are not understood. Here we reveal their dynamic expression during embryo myogenesis and uncover the concerted negative regulation of BAF60a and BAF60b by the muscle-specific microRNAs (myomiRs) miR-133 and miR-1/206 during somite differentiation. MicroRNA inhibition in chick embryos leads to increased BAF60a or BAF60b levels, a concomitant switch in BAF/Brg1 subunit composition and delayed myogenesis. The phenotypes are mimicked by sustained BAF60a or BAF60b expression and are rescued by morpholino knockdown of BAF60a or BAF60b. This suggests that myomiRs contribute to select BAF60c for incorporation into the Brg1 complex by specifically targeting the alternative variants BAF60a and BAF60b during embryo myogenesis, and reveals that interactions between tissue-specific non-coding RNAs and chromatin remodeling factors confer robustness to mesodermal lineage determination.
authors: School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
authors: Katarzyna
authors: K
authors: Goljanek-Whysall
authors: School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
authors: Gi Fay
authors: GF
authors: Mok
authors: School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
authors: Abdulmajeed
authors: A
authors: Fahad Alrefaei
authors: School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
authors: Niki
authors: N
authors: Kennerley
authors: School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
authors: Grant N
authors: GN
authors: Wheeler
authors: School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK a.munsterberg@uea.ac.uk.
authors: Andrea
authors: A
authors: Münsterberg
mesh_terms: D000818:Animals; D001483:Base Sequence; D002642:Chick Embryo; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D060172:Morpholinos / Q000494:pharmacology; D024510:Muscle Development / Q000235:genetics*; D041681:NIH 3T3 Cells; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D019170:Somites / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D035683:MicroRNAs; D060172:Morpholinos; D020033:Protein Isoforms; D021122:Protein Subunits; D014157:Transcription Factors
keywords: BAF chromatin remodeling complex; Brg1; Chick embryo; Smarcd; Somite myogenesis; miR-1; miR-133; miR-206