Noncanonical Genomic Imprinting Effects in Offspring
Noncanonical Genomic Imprinting Effects in Offspring
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DOI：
10.1016/j.celrep.2015.07.017
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发表时间：
2015-08-11
期刊：
影响因子：
8.8
通讯作者：
Gregg, Christopher
中科院分区：
文献类型：
--
作者：
Bonthuis, Paul J.;Huang, Wei-Chao;Gregg, Christopher
在这里，我们描述了一种基于 RNA 测序 (RNA-seq) 的方法，该方法可以在组织水平上准确检测哪怕是轻微的母本或父本等位基因表达偏差，我们称之为非典型基因组印记效应。我们对雌性小鼠大脑的弓状核（ARN）和中缝背核以及骨骼肌（中胚层）和肝脏（内胚层）的印迹进行了分析。我们的研究揭示了数百种非典型常染色体和 X 连锁印记效应。非规范印记具有高度组织特异性，并且在 ARN 中丰富，但在肝脏中很少见。这些效应在不同的遗传背景下是可重复的，并且与等位基因特异性染色质相关。利用新生RNA的原位杂交，我们发现具有组织水平等位基因偏差的常染色体非典型印记基因在体内大脑神经元亚群中表现出等位基因特异性表达效应。我们定义了调节单胺信号传导的非经典印记基因，并确定这些效应会影响遗传突变对后代行为的影响。
Here, we describe an RNA-sequencing (RNA-seq)-based approach that accurately detects even modest maternal or paternal allele expression biases at the tissue level, which we call noncanonical genomic imprinting effects. We profile imprinting in the arcuate nucleus (ARN) and dorsal raphe nucleus of the female mouse brain as well as skeletal muscle (mesodermal) and liver (endodermal). Our study uncovers hundreds of noncanonical autosomal and X-linked imprinting effects. Noncanonical imprinting is highly tissue-specific and enriched in the ARN, but rare in the liver. These effects are reproducible across different genetic backgrounds and associated with allele-specific chromatin. Using in situ hybridization for nascent RNAs, we discover that autosomal noncanonical imprinted genes with a tissue-level allele bias exhibit allele-specific expression effects in subpopulations of neurons in the brain in vivo. We define noncanonical imprinted genes that regulate monoamine signaling and determine that these effects influence the impact of inherited mutations on offspring behavior.