Genome-wide survey by ChIP-seq reveals YY1 regulation of lincRNAs in skeletal myogenesis

EMBO J. 2013 Oct 2;32(19):2575-88. doi: 10.1038/emboj.2013.182. Epub 2013 Aug 13.

Abstract

Skeletal muscle differentiation is orchestrated by a network of transcription factors, epigenetic regulators, and non-coding RNAs. The transcription factor Yin Yang 1 (YY1) silences multiple target genes in myoblasts (MBs) by recruiting Ezh2 (Enhancer of Zeste Homologue2). To elucidate genome-wide YY1 binding in MBs, we performed chromatin immunoprecipitation (ChIP)-seq and found 1820 specific binding sites in MBs with a large portion residing in intergenic regions. Detailed analysis demonstrated that YY1 acts as an activator for many loci in addition to its known repressor function. No significant co-occupancy was found between YY1 and Ezh2, suggesting an additional Ezh2-independent function for YY1 in MBs. Further analysis of intergenic binding sites showed that YY1 potentially regulates dozens of large intergenic non-coding RNAs (lincRNAs), whose function in myogenesis is underexplored. We characterized a novel muscle-associated lincRNA (Yam-1) that is positively regulated by YY1. Yam-1 is downregulated upon differentiation and acts as an inhibitor of myogenesis. We demonstrated that Yam-1 functions through in cis regulation of miR-715, which in turn targets Wnt7b. Our findings not only provide the first genome-wide picture of YY1 association in muscle cells, but also uncover the functional role of lincRNA Yam-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Line
  • Cells, Cultured
  • Chromatin Immunoprecipitation
  • Genome
  • Mice
  • Mice, Inbred C57BL
  • Muscle Development / physiology*
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / physiology*
  • Myoblasts / cytology
  • Myoblasts / physiology*
  • RNA, Long Noncoding / physiology*
  • YY1 Transcription Factor / physiology*

Substances

  • RNA, Long Noncoding
  • YY1 Transcription Factor
  • Yy1 protein, mouse