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. |