Genome-wide survey by ChIP-seq reveals YY1 regulation of lincRNAs in skeletal myogenesis.
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.
Department of Chemical Pathology, Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
Leina
L
Lu
Kun
K
Sun
Xiaona
X
Chen
Yu
Y
Zhao
Lijun
L
Wang
Liang
L
Zhou
Hao
H
Sun
Huating
H
Wang
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D016678:Genome; D051379:Mice; D008810:Mice, Inbred C57BL; D024510:Muscle Development / Q000502:physiology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*; D032446:Myoblasts / Q000166:cytology / Q000502:physiology*; D062085:RNA, Long Noncoding / Q000502:physiology*; D050986:YY1 Transcription Factor / Q000502:physiology*
D062085:RNA, Long Noncoding; D050986:YY1 Transcription Factor; C494699:Yy1 protein, mouse