Ahn Jinsoo, Lee Joonbum, Kim Dong-Hwan, Hwang In-Sul, Park Mi-Ryung, Cho In-Cheol, Hwang Seongsoo, Lee Kichoon
Functional Genomics Laboratory, Department of Animal Sciences, The Ohio State University, Columbus, OH, United States.
The Ohio State University Interdisciplinary Human Nutrition Program, The Ohio State University, Columbus, OH, United States.
Front Genet. 2022 Jul 22;13:920641. doi: 10.3389/fgene.2022.920641. eCollection 2022.
In mammals, genomic imprinting operates gene silencing mechanisms. Although conservation of the imprinting mechanism at the / locus has been generally described in pigs, tissue-specific imprinting at the transcript level, monoallelic-to-biallelic conversion, and spatio-temporal chromatin reorganization remain largely uninvestigated. Here, we delineate spatially regulated imprinting of transcripts, age-dependent hepatic mono- to biallelic conversion, and reorganization of topologically associating domains at the porcine locus for better translation to human and animal research. Whole-genome bisulfite sequencing (WGBS) and RNA sequencing (RNA-seq) of normal and parthenogenetic porcine embryos revealed the paternally hypermethylated differentially methylated region and paternal expression of . Using a polymorphism-based approach and omics datasets from chromatin immunoprecipitation sequencing (ChIP-seq), whole-genome sequencing (WGS), RNA-seq, and Hi-C, regulation of during development was analyzed. Regulatory elements in the liver were distinguished from those in the muscle where the porcine transcript was monoallelically expressed. The transcript from the liver was biallelically expressed at later developmental stages in both pigs and humans. Chromatin interaction was less frequent in the adult liver compared to the fetal liver and skeletal muscle. The duration of genomic imprinting effects within the / locus might be reduced in the liver with biallelic conversion through alternative promoter usage and chromatin remodeling. Our integrative omics analyses of genome, epigenome, and transcriptome provided a comprehensive view of imprinting status at the / cluster.
在哺乳动物中，基因组印记发挥着基因沉默机制的作用。尽管猪的/位点印记机制的保守性已被普遍描述，但转录水平的组织特异性印记、单等位基因到双等位基因的转换以及时空染色质重组在很大程度上仍未得到研究。在此，我们描绘了猪/位点转录本的空间调控印记、年龄依赖性肝脏单等位基因到双等位基因的转换以及拓扑相关结构域的重组，以便更好地转化为人类和动物研究。正常和孤雌生殖猪胚胎的全基因组亚硫酸氢盐测序（WGBS）和RNA测序（RNA-seq）揭示了父本超甲基化的差异甲基化区域和/的父本表达。使用基于多态性的方法以及来自染色质免疫沉淀测序（ChIP-seq）、全基因组测序（WGS）、RNA-seq和Hi-C的组学数据集，分析了/在发育过程中的调控。肝脏中的调控元件与肌肉中的调控元件不同，在肌肉中猪/转录本是单等位基因表达的。猪和人类肝脏中的转录本在发育后期均为双等位基因表达。与胎儿肝脏和骨骼肌相比，成年肝脏中的染色质相互作用频率较低。通过替代启动子使用和染色质重塑，肝脏中双等位基因转换可能会缩短/位点内基因组印记效应的持续时间。我们对基因组、表观基因组和转录组的综合组学分析提供了/簇印记状态的全面视图。
