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Publication : De Novo Reconstruction of Adipose Tissue Transcriptomes Reveals Long Non-coding RNA Regulators of Brown Adipocyte Development.

First Author  Alvarez-Dominguez JR Year  2015
Journal  Cell Metab Volume  21
Issue  5 Pages  764-776
PubMed ID  25921091 Mgi Jnum  J:272999
Mgi Id  MGI:6286426 Doi  10.1016/j.cmet.2015.04.003
Citation  Alvarez-Dominguez JR, et al. (2015) De Novo Reconstruction of Adipose Tissue Transcriptomes Reveals Long Non-coding RNA Regulators of Brown Adipocyte Development. Cell Metab 21(5):764-776
abstractText  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 approximately 1,500 lncRNAs, including 127 BAT-restricted loci induced during differentiation and often targeted by key regulators PPARgamma, C/EBPalpha, and C/EBPbeta. 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.
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