Linc-YY1 promotes myogenic differentiation and muscle regeneration through an interaction with the transcription factor YY1

Liang Zhou, Kun Sun, Yu Zhao, Suyang Zhang, Xuecong Wang, Yuying Li, Leina Lu, Xiaona Chen, Fengyuan Chen, Xichen Bao, Xihua Zhu, Lijun Wang, Ling-Yin Tang, Miguel A. Esteban, Chi-Chiu Wang, Ralf Jauch, Hao Sun () and Huating Wang ()
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Liang Zhou: Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong
Kun Sun: Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong
Yu Zhao: Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong
Suyang Zhang: Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong
Xuecong Wang: Genome Regulation Laboratory, Drug Discovery Pipeline, Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences
Yuying Li: Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong
Leina Lu: Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong
Xiaona Chen: Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong
Fengyuan Chen: Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong
Xichen Bao: Laboratory of Chromatin and Human Disease, Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences
Xihua Zhu: Laboratory of Chromatin and Human Disease, Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences
Lijun Wang: Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong
Ling-Yin Tang: Prince of Wales Hospital, The Chinese University of Hong Kong
Miguel A. Esteban: Laboratory of Chromatin and Human Disease, Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences
Chi-Chiu Wang: Prince of Wales Hospital, The Chinese University of Hong Kong
Ralf Jauch: Genome Regulation Laboratory, Drug Discovery Pipeline, Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences
Hao Sun: Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong
Huating Wang: Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong

Nature Communications, 2015, vol. 6, issue 1, 1-16

Abstract: Abstract Little is known how lincRNAs are involved in skeletal myogenesis. Here we describe the discovery of Linc-YY1 from the promoter of the transcription factor (TF) Yin Yang 1 (YY1) gene. We demonstrate that Linc-YY1 is dynamically regulated during myogenesis in vitro and in vivo. Gain or loss of function of Linc-YY1 in C2C12 myoblasts or muscle satellite cells alters myogenic differentiation and in injured muscles has an impact on the course of regeneration. Linc-YY1 interacts with YY1 through its middle domain, to evict YY1/Polycomb repressive complex (PRC2) from target promoters, thus activating the gene expression in trans. In addition, Linc-YY1 also regulates PRC2-independent function of YY1. Finally, we identify a human Linc-YY1 orthologue with conserved function and show that many human and mouse TF genes are associated with lincRNAs that may modulate their activity. Altogether, we show that Linc-YY1 regulates skeletal myogenesis and uncover a previously unappreciated mechanism of gene regulation by lincRNA.

Date: 2015
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DOI: 10.1038/ncomms10026

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