De Novo Reconstruction of Adipose Tissue Transcriptomes Reveals Long Non-coding RNA Regulators of Brown Adipocyte Development.
De Novo Reconstruction of Adipose Tissue Transcriptomes Reveals Long Non-coding RNA Regulators of Brown Adipocyte Development.
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脂肪组织转录组的从头重建揭示了棕色脂肪细胞发育的长无编码RNA调节剂。
DOI：
10.1016/j.cmet.2015.04.003
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发表时间：
2015-05-05
期刊：
影响因子：
29
通讯作者：
Sun L
中科院分区：
文献类型：
--
作者：
Alvarez-Dominguez JR;Bai Z;Xu D;Yuan B;Lo KA;Yoon MJ;Lim YC;Knoll M;Slavov N;Chen S;Peng C;Lodish HF;Sun L
棕色脂肪组织（BAT）通过促进非偶联呼吸的能量消耗来防止肥胖。为了揭示BAT特异性长链非编码RNA（lncRNA），我们使用RNA-seq重建了小鼠棕色脂肪、腹股沟白色脂肪和附睾白色脂肪的从头转录组，并鉴定了约1500个lncRNA，包括127个BAT限制性基因座分化期间诱导的，并且通常是关键调节因子PPARγ、C/EBPα和C/EBPβ的靶点。其中之一，lnc-BATE 1，是建立和维持BAT身份和产热能力所必需的。lnc-BATE 1抑制损害棕色脂肪和白色脂肪基因的抑制的同时激活，并部分获救的外源lnc-BATE 1与突变的siRNA靶向位点，证明了反式的功能。我们表明，lnc-BATE 1结合异质核核糖核蛋白U，两者都是棕色脂肪形成所需的。我们的工作为脂肪储存选择性lncRNA的研究提供了一个注释目录，可在线获得，并建立了lnc-BATE 1作为BAT发育和生理学的新型调节因子。
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 ~1500 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, available online, and establishes lnc-BATE1 as a novel regulator of BAT development and physiology.
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影响因子：
14.9
作者：
Flicek P;Amode MR;Barrell D;Beal K;Billis K;Brent S;Carvalho-Silva D;Clapham P;Coates G;Fitzgerald S;Gil L;Girón CG;Gordon L;Hourlier T;Hunt S;Johnson N;Juettemann T;Kähäri AK;Keenan S;Kulesha E;Martin FJ;Maurel T;McLaren WM;Murphy DN;Nag R;Overduin B;Pignatelli M;Pritchard B;Pritchard E;Riat HS;Ruffier M;Sheppard D;Taylor K;Thormann A;Trevanion SJ;Vullo A;Wilder SP;Wilson M;Zadissa A;Aken BL;Birney E;Cunningham F;Harrow J;Herrero J;Hubbard TJ;Kinsella R;Muffato M;Parker A;Spudich G;Yates A;Zerbino DR;Searle SM
通讯作者：
Searle SM
影响因子：
16.8
作者：
Kaneko, Syuzo;Son, Jinsook;Shen, Steven S.;Reinberg, Danny;Bonasio, Roberto
通讯作者：
Bonasio, Roberto
DOI：
10.1093/bioinformatics/btr209
发表时间：
2011-07-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Lin MF;Jungreis I;Kellis M
通讯作者：
Kellis M
影响因子：
4.8
作者：
Hamann, A;Flier, JS;Lowell, BB
通讯作者：
Lowell, BB
影响因子：
10.5
作者：
Cabili, Moran N.;Trapnell, Cole;Rinn, John L.
通讯作者：
Rinn, John L.