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A Long noncoding RNA transcriptional regulatory circuit drives thermogenic adipocyte differentiation

机译:长的非编码RNA转录调控电路驱动产热脂肪细胞分化

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摘要

Brown and beige/brite fats generate heat via uncoupled respiration to defend against cold. The total mass and activity of thermogenic adipose tissues are also tightly linked to systemic energy and nutrient homeostasis. Despite originating from distinct progenitors, brown and beige adipocytes acquire remarkably similar molecular and metabolic characteristics during differentiation through the action of a network of transcription factors and cofactors. How this regulatory network interfaces with long noncoding RNAs (lncRNAs), an emerging class of developmental regulators, remains largely unexplored. Here, we globally profiled lncRNA gene expression during thermogenic adipocyte formation and identified Brown fat lncRNA 1 (Blnc1) as a nuclear lncRNA that promotes brown and beige adipocyte differentiation and function. Blnc1 forms a ribonucleoprotein complex with transcription factor EBF2 to stimulate the thermogenic gene program. Further, Blnc1 itself is a target of EBF2, thereby forming a feedforward regulatory loop to drive adipogenesis toward thermogenic phenotype.
机译:棕色和米色/棕褐色脂肪通过不相关的呼吸作用产生热量,从而抵御寒冷。生热脂肪组织的总质量和活性也与全身能量和营养稳态保持紧密联系。尽管棕色和米色脂肪细胞起源于不同的祖细胞,但它们在分化过程中通过转录因子和辅因子网络的作用获得了非常相似的分子和代谢特征。该调节网络如何与长的非编码RNA(lncRNA)(新兴的一类发育调节剂)对接,目前尚待探索。在这里,我们全球性剖析了产热脂肪细胞形成过程中lncRNA基因的表达,并确定了棕色脂肪lncRNA 1(Blnc1)作为促进棕色和米色脂肪细胞分化和功能的核lncRNA。 Blnc1与转录因子EBF2形成核糖核蛋白复合物,以刺激热基因程序。此外,Blnc1本身是EBF2的靶标,从而形成前馈调节环以驱动成脂向生热表型发展。

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