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 diff...

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Main Authors: Tengfei Xiao, Lihui Liu, Hongling Li, Yu Sun, Huaxia Luo, Tangping Li, Shihua Wang, Stephen Dalton, Robert Chunhua Zhao, Runsheng Chen
Format: Article
Language:English
Published: Elsevier 2015-11-01
Series:Stem Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2213671115002696
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author Tengfei Xiao
Lihui Liu
Hongling Li
Yu Sun
Huaxia Luo
Tangping Li
Shihua Wang
Stephen Dalton
Robert Chunhua Zhao
Runsheng Chen
author_facet Tengfei Xiao
Lihui Liu
Hongling Li
Yu Sun
Huaxia Luo
Tangping Li
Shihua Wang
Stephen Dalton
Robert Chunhua Zhao
Runsheng Chen
author_sort Tengfei Xiao
collection DOAJ
description 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.
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spelling doaj.art-f9abc259158a482ca468e6d90cb42e7b2022-12-21T23:52:14ZengElsevierStem Cell Reports2213-67112015-11-015585686510.1016/j.stemcr.2015.09.007Long Noncoding RNA ADINR Regulates Adipogenesis by Transcriptionally Activating C/EBPαTengfei Xiao0Lihui Liu1Hongling Li2Yu Sun3Huaxia Luo4Tangping Li5Shihua Wang6Stephen Dalton7Robert Chunhua Zhao8Runsheng Chen9Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, ChinaKey Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, ChinaCenter 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, ChinaKey Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, ChinaKey Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, ChinaCenter 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, ChinaCenter 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, ChinaPaul 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, USACenter 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, ChinaKey Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, ChinaC/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.http://www.sciencedirect.com/science/article/pii/S2213671115002696
spellingShingle Tengfei Xiao
Lihui Liu
Hongling Li
Yu Sun
Huaxia Luo
Tangping Li
Shihua Wang
Stephen Dalton
Robert Chunhua Zhao
Runsheng Chen
Long Noncoding RNA ADINR Regulates Adipogenesis by Transcriptionally Activating C/EBPα
Stem Cell Reports
title Long Noncoding RNA ADINR Regulates Adipogenesis by Transcriptionally Activating C/EBPα
title_full Long Noncoding RNA ADINR Regulates Adipogenesis by Transcriptionally Activating C/EBPα
title_fullStr Long Noncoding RNA ADINR Regulates Adipogenesis by Transcriptionally Activating C/EBPα
title_full_unstemmed Long Noncoding RNA ADINR Regulates Adipogenesis by Transcriptionally Activating C/EBPα
title_short Long Noncoding RNA ADINR Regulates Adipogenesis by Transcriptionally Activating C/EBPα
title_sort long noncoding rna adinr regulates adipogenesis by transcriptionally activating c ebpα
url http://www.sciencedirect.com/science/article/pii/S2213671115002696
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