Long Noncoding RNA ADINR Regulates Adipogenesis by Transcriptionally Activating C/EBPα

被引：234

作者：

Xiao, Tengfei ^{[1
,2
,3
]}

Liu, Lihui ^{[1
,2
,5
]}

Li, Hongling ^{[4
]}

Sun, Yu ^{[1
,2
,5
]}

Luo, Huaxia ^{[1
,2
,5
]}

Li, Tangping ^{[4
]}

Wang, Shihua ^{[4
]}

Dalton, Stephen ^{[6
]}

Zhao, Robert Chunhua ^{[4
]}

Chen, Runsheng ^{[1
,2
]}

机构：

[1] Chinese Acad Sci, Inst Biophys, Key Lab RNA Biol, Beijing 100101, Peoples R China

[2] Chinese Acad Sci, Inst Biophys, Key Lab Noncoding RNA, Beijing 100101, Peoples R China

[3] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA

[4] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Peking Union Med Coll, Ctr Excellence Tissue Engn,Inst Basic Med Sci,Sch, Beijing 100005, Peoples R China

[5] Chinese Acad Sci, Grad Sch, Beijing 100080, Peoples R China

[6] Univ Georgia, Dept Biochem & Mol Biol, Paul D Coverdell Ctr Biomed & Hlth Sci, Athens, GA 30602 USA

来源：

STEM CELL REPORTS | 2015年 / 5卷 / 05期

基金：

中国国家自然科学基金;

关键词：

PPAR-GAMMA; STEM-CELLS; IN-VITRO; CHROMATIN; EXPRESSION; REVEALS; NOISE; MAPS; DNA;

D O I：

10.1016/j.stemcr.2015.09.007

中图分类号：

Q813 [细胞工程];

学科分类号：

100113 [医学细胞生物学];

摘要：

C/EBP alpha is a critical transcriptional regulator of adipogenesis. HowC/EBP alpha transcriptionis 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 similar to 450 bp upstream of the C/EBP alpha gene, that orchestrates C/EBP alpha transcriptionin vivo. Depletion of ADINR leads to a severe adipogenic defect that is rescued by overexpression of C/EBP alpha. 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/EBP alpha 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/EBP alpha in cis.

引用

页码：856 / 865

页数：10

共 38 条

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A bivalent chromatin structure marks key developmental genes in embryonic stem cells [J].