Early-life undernutrition induces enhancer RNA remodeling in mice liver.
Early-life undernutrition induces enhancer RNA remodeling in mice liver.
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DOI：
10.1186/s13072-021-00392-w
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发表时间：
2021-03-31
影响因子：
3.9
通讯作者：
Huang H
中科院分区：
文献类型：
--
作者：
Wang Y;Mao Y;Zhao Y;Yi X;Ding G;Yu C;Sheng J;Liu X;Meng Y;Huang H
母体蛋白质限制饮食（PRD）增加了成年期代谢功能障碍的风险，其在后代早期生活中的机制仍然知之甚少。除了遗传因素外，表观遗传机制对于提供表型可塑性以应对环境状况和传播至关重要。增强子相关非编码RNA（eRNA）转录作为增强子激活的一个强有力的指标，在介导增强子功能和基因转录中具有潜在的作用。使用新生RNA（包括eRNA和总RNA测序数据）的全局连续测序（GRO-seq），我们发现早期营养不良导致小鼠肝脏增强子活性重塑。差异表达的新生活性基因在代谢途径中富集。此外，我们的工作检测到大量的高置信度增强子基于eRNA转录在4周龄和7周龄分别。重要的是，除了约1000个重塑增强子外，早期营养不良诱导增强子活性的不稳定性，其在4周内下降，并在成年期增加。eRNA转录主要参与一些重要代谢酶的调节，提示代谢功能障碍与增强子转录调控之间存在联系。我们发现了一种新的eRNA，它与昼夜节律基因Cry 1的表达呈正相关，并增加了表观遗传辅因子p300的结合。我们的研究揭示了代谢功能障碍机制的新见解。生命早期的增强子活性作用于代谢相关基因，导致代谢紊乱的易感性增加。在线版本包含补充材料，可通过10.1186/s13072-021-00392-w获得。
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. The online version contains supplementary material available at 10.1186/s13072-021-00392-w.
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影响因子：
1.9
作者：
Nallagangula KS;Shashidhar KN;Lakshmaiah V;Muninarayana C
通讯作者：
Muninarayana C
影响因子：
8.2
作者：
Martin-Gronert MS;Fernandez-Twinn DS;Bushell M;Siddle K;Ozanne SE
通讯作者：
Ozanne SE
影响因子：
64.5
作者：
Levine M
通讯作者：
Levine M
DOI：
10.1590/s0100-879x2010007500113
发表时间：
2010-11-01
影响因子：
2.3
作者：
Mesquita, F.F.;Gontijo, J.A.R.;Boer, P.A.
通讯作者：
Boer, P.A.
影响因子：
3.2
作者：
Herring, Cassandra M.;Bazer, Fuller W.;Wu, Guoyao
通讯作者：
Wu, Guoyao