Long Noncoding RNA ADINR Regulates Adipogenesis by Transcriptionally Activating C/EBPα.
C/EBPα is a critical transcriptional regulator of adipogenesis. How C/EBPα transcription is itself regulated is poorly understood, however, and remains a key question that needs to be addressed for a complete understanding of adipogenic development. Here, we identify a lncRNA, ADINR (adipogenic differentiation induced noncoding RNA), transcribed from a position ∼450 bp upstream of the C/EBPα gene, that orchestrates C/EBPα transcription in vivo. Depletion of ADINR leads to a severe adipogenic defect that is rescued by overexpression of C/EBPα. Moreover, we reveal that ADINR RNA specifically binds to PA1 and recruits MLL3/4 histone methyl-transferase complexes so as to increase H3K4me3 and decrease H3K27me3 histone modification in the C/EBPα locus during adipogenesis. These results show that ADINR plays important roles in regulating the differentiation of human mesenchymal stem cells into adipocytes by modulating C/EBPα in cis.
Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; Key Laboratory of Non-coding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Harvard School of Public Health, Boston, MA 02215, USA.
Tengfei
T
Xiao
Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; Key Laboratory of Non-coding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; Graduate School of the Chinese Academy of Sciences, Beijing 100080, China.
Lihui
L
Liu
Center of Excellence in Tissue Engineering, Institute of Basic Medical Sciences, School of Basic Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100005, China.
Hongling
H
Li
Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; Key Laboratory of Non-coding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; Graduate School of the Chinese Academy of Sciences, Beijing 100080, China.
Yu
Y
Sun
Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; Key Laboratory of Non-coding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; Graduate School of the Chinese Academy of Sciences, Beijing 100080, China.
Huaxia
H
Luo
Center of Excellence in Tissue Engineering, Institute of Basic Medical Sciences, School of Basic Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100005, China.
Tangping
T
Li
Center of Excellence in Tissue Engineering, Institute of Basic Medical Sciences, School of Basic Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100005, China.
Shihua
S
Wang
Paul D. Coverdell Center for Biomedical and Health Sciences, Department of Biochemistry and Molecular Biology, The University of Georgia, 500 D.W. Brooks Drive, Athens, GA 30602, USA.
Stephen
S
Dalton
Center of Excellence in Tissue Engineering, Institute of Basic Medical Sciences, School of Basic Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100005, China. Electronic address: zhaochunhua@vip.163.com.
Robert Chunhua
RC
Zhao
Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; Key Laboratory of Non-coding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: rschen@ibp.ac.cn.
Runsheng
R
Chen
D050156:Adipogenesis; D000273:Adipose Tissue / Q000166:cytology; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D006657:Histones / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D008780:Methyltransferases / Q000378:metabolism; D011485:Protein Binding; D062085:RNA, Long Noncoding / Q000235:genetics*; D015533:Transcriptional Activation
D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; C000610076:CEBPA-DT long noncoding RNA, human; D006657:Histones; D062085:RNA, Long Noncoding; D008780:Methyltransferases