De Novo Reconstruction of Adipose Tissue Transcriptomes Reveals Long Non-coding RNA Regulators of Brown Adipocyte Development.
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.
Whitehead Institute for Biomedical Research, Cambridge, MA, 02142, USA.|Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02142, USA.
Juan R
JR
Alvarez-Dominguez
Cardiovascular and Metabolic Disorders Program, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore.
Zhiqiang
Z
Bai
Cardiovascular and Metabolic Disorders Program, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore.
Dan
D
Xu
Whitehead Institute for Biomedical Research, Cambridge, MA, 02142, USA.
Bingbing
B
Yuan
Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore.
Kinyui Alice
KA
Lo
Cardiovascular and Metabolic Disorders Program, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore.
Myeong Jin
MJ
Yoon
Cardiovascular and Metabolic Disorders Program, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore.
Yen Ching
YC
Lim
Whitehead Institute for Biomedical Research, Cambridge, MA, 02142, USA.
Marko
M
Knoll
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02142, USA.
Nikolai
N
Slavov
MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, 210061, China.
Shuai
S
Chen
Division of Bioengineering, Nanyang Technological University, 70 Nanyang Drive, Singapore 637457.
Chen
C
Peng
Whitehead Institute for Biomedical Research, Cambridge, MA, 02142, USA.|Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02142, USA.
Harvey F
HF
Lodish
Cardiovascular and Metabolic Disorders Program, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore.|Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore.
Lei
L
Sun
D052437:Adipocytes, Brown / Q000166:cytology* / Q000378:metabolism; D050156:Adipogenesis; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000378:metabolism; D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D006801:Humans; D051379:Mice; D062085:RNA, Long Noncoding / Q000235:genetics*; D022722:Thermogenesis; D015533:Transcriptional Activation; D059467:Transcriptome
D062085:RNA, Long Noncoding