Myogenic microRNA expression requires ATP-dependent chromatin remodeling enzyme function.
Knockdown of the Brg1 ATPase subunit of SWI/SNF chromatin remodeling enzymes in developing zebrafish caused stunted tail formation and altered sarcomeric actin organization, which phenocopies the loss of the microRNA processing enzyme Dicer, or the knockdown of myogenic microRNAs. Furthermore, myogenic microRNA expression and differentiation was blocked in Brg1 conditional myoblasts differentiated ex vivo. The binding of Brg1 upstream of myogenic microRNA sequences correlated with MyoD binding and accessible chromatin structure in satellite cells and myofibers, and it was required for chromatin accessibility and microRNA expression in a tissue culture model for myogenesis. The results implicate ATP-dependent chromatin remodelers in myogenic microRNA gene regulation.
Mallappa
Chandrashekara
C
Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Nasipak
Brian T
BT
Etheridge
Letitiah
L
Androphy
Elliot J
EJ
Jones
Stephen N
SN
Sagerström
Charles G
CG
Ohkawa
Yasuyuki
Y
Imbalzano
Anthony N
AN
D048868:Adaptor Proteins, Signal Transducing; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D024510:Muscle Development / Q000235:genetics*; D032446:Myoblasts / Q000166:cytology / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000033:anatomy & histology / Q000196:embryology / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D002843:Chromatin; D035683:MicroRNAs; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense; D014157:Transcription Factors; D029961:Zebrafish Proteins; C516328:smarca4a protein, zebrafish; D000255:Adenosine Triphosphate; D043244:Ribonuclease III; C513194:Smarca4 protein, mouse; D004265:DNA Helicases