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首页> 外文期刊>Epigenetics & Chromatin >Early-life undernutrition induces enhancer RNA remodeling in mice liver
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Early-life undernutrition induces enhancer RNA remodeling in mice liver

机译:早期营养不良诱导小鼠肝脏改造的增强子RNA重塑

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Maternal protein restriction diet (PRD) increases the risk of metabolic dysfunction in adulthood, the mechanisms during the early life of offspring are still poorly understood. Apart from genetic factors, epigenetic mechanisms are crucial to offer phenotypic plasticity in response to environmental situations and transmission. Enhancer-associated noncoding RNAs (eRNAs) transcription serves as a robust indicator of enhancer activation, and have potential roles in mediating enhancer functions and gene transcription. Using global run-on sequencing (GRO-seq) of nascent RNA including eRNA and total RNA sequencing data, we show that early-life undernutrition causes remodeling of enhancer activity in mouse liver. Differentially expressed nascent active genes were enriched in metabolic pathways. Besides, our work detected a large number of high confidence enhancers based on eRNA transcription at the ages of 4?weeks and 7?weeks, respectively. Importantly, except for?~?1000 remodeling enhancers, the early-life undernutrition induced instability of enhancer activity which decreased in 4?weeks and increased in adulthood. eRNA transcription mainly contributes to the regulation of some important metabolic enzymes, suggesting a link between metabolic dysfunction and enhancer transcriptional control. We discovered a novel eRNA that is positively correlated to the expression of circadian gene Cry1 with increased binding of epigenetic cofactor p300. Our study reveals novel insights into mechanisms of metabolic dysfunction. Enhancer activity in early life acts on metabolism-associated genes, leading to the increased susceptibility of metabolic disorders.
机译:母体蛋白质限制性饮食(PRD)增加了成年期代谢功能障碍的风险,后代早期寿命的机制仍然不知所措。除了遗传因素外,表观遗传机制对于响应环境情况和传播而提供表型可塑性至关重要。增强子相关的非分子RNA(ERNAS)转录用作增强剂激活的鲁棒指标,并且在介导增强剂功能和基因转录中具有潜在的作用。使用Nascent RNA的全局续集测序(GRO-SEQ),包括ERNA和总RNA测序数据,我们表明早期损失导致小鼠肝脏中增强剂活性的重塑。差异表达的新生活性基因富集在代谢途径中。此外,我们的工作分别检测到基于4?周和7周龄的erna转录的大量高置信增强剂。重要的是,除了?〜?1000重塑增强剂,早期营养不良诱导的增强剂活性的不稳定,在4?周内减少并在成年期增加。 erna转录主要有助于调节一些重要的代谢酶,表明代谢功能障碍和增强剂转录控制之间的联系。我们发现了一种新的erna,它与昼夜节律Cofactor p300的增加的结合呈正相关。我们的研究揭示了对代谢功能障碍机制的新颖见解。早期生命中的增强剂活性作用于新陈代谢相关基因,导致代谢障碍的易感性增加。

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