TY - JOUR
T1 - De Novo Reconstruction of Adipose Tissue Transcriptomes Reveals Long Non-coding RNA Regulators of Brown Adipocyte Development
AU - Alvarez-Dominguez, Juan R.
AU - Bai, Zhiqiang
AU - Xu, Dan
AU - Yuan, Bingbing
AU - Lo, Kinyui Alice
AU - Yoon, Myeong Jin
AU - Lim, Yen Ching
AU - Knoll, Marko
AU - Slavov, Nikolai
AU - Chen, Shuai
AU - Chen, Peng
AU - Lodish, Harvey F.
AU - Sun, Lei
N1 - Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/5/5
Y1 - 2015/5/5
N2 - Brown adipose tissue (BAT) protects against obesity by promoting energy expenditure via uncoupled respiration. To uncover BAT-specific long non-coding RNAs (lncRNAs), we used RNA-seq to reconstruct de novo transcriptomes of mouse brown, inguinal white, and epididymal white fat and identified ∼1,500 lncRNAs, including 127 BAT-restricted loci induced during differentiation and often targeted by key regulators PPARγ, C/EBPα, and C/EBPβ. One of them, lnc-BATE1, is required for establishment and maintenance of BAT identity and thermogenic capacity. lnc-BATE1 inhibition impairs concurrent activation of brown fat and repression of white fat genes and is partially rescued by exogenous lnc-BATE1 with mutated siRNA-targeting sites, demonstrating a function in trans. We show that lnc-BATE1 binds heterogeneous nuclear ribonucleoprotein U and that both are required for brown adipogenesis. Our work provides an annotated catalog for the study of fat depot-selective lncRNAs and establishes lnc-BATE1 as a regulator of BAT development and physiology. Alvarez-Dominguez et al. report an annotated catalog of lncRNAs active across adipose tissues, uncovering >100 brown fat-selective and dynamically regulated lncRNAs. One of them, lnc-BATE1, acts in trans to sustain the core brown fat gene program and repress white fat genes, modulating development and maintenance of brown thermogenic adipocytes.
AB - Brown adipose tissue (BAT) protects against obesity by promoting energy expenditure via uncoupled respiration. To uncover BAT-specific long non-coding RNAs (lncRNAs), we used RNA-seq to reconstruct de novo transcriptomes of mouse brown, inguinal white, and epididymal white fat and identified ∼1,500 lncRNAs, including 127 BAT-restricted loci induced during differentiation and often targeted by key regulators PPARγ, C/EBPα, and C/EBPβ. One of them, lnc-BATE1, is required for establishment and maintenance of BAT identity and thermogenic capacity. lnc-BATE1 inhibition impairs concurrent activation of brown fat and repression of white fat genes and is partially rescued by exogenous lnc-BATE1 with mutated siRNA-targeting sites, demonstrating a function in trans. We show that lnc-BATE1 binds heterogeneous nuclear ribonucleoprotein U and that both are required for brown adipogenesis. Our work provides an annotated catalog for the study of fat depot-selective lncRNAs and establishes lnc-BATE1 as a regulator of BAT development and physiology. Alvarez-Dominguez et al. report an annotated catalog of lncRNAs active across adipose tissues, uncovering >100 brown fat-selective and dynamically regulated lncRNAs. One of them, lnc-BATE1, acts in trans to sustain the core brown fat gene program and repress white fat genes, modulating development and maintenance of brown thermogenic adipocytes.
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U2 - 10.1016/j.cmet.2015.04.003
DO - 10.1016/j.cmet.2015.04.003
M3 - Article
C2 - 25921091
AN - SCOPUS:84928192649
SN - 1550-4131
VL - 21
SP - 764
EP - 776
JO - Cell Metabolism
JF - Cell Metabolism
IS - 5
ER -