AUTHOR=Ahn Jinsoo , Lee Joonbum , Kim Dong-Hwan , Hwang In-Sul , Park Mi-Ryung , Cho In-Cheol , Hwang Seongsoo , Lee Kichoon 

TITLE=Loss of Monoallelic Expression of IGF2 in the Adult Liver Via Alternative Promoter Usage and Chromatin Reorganization

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.920641

DOI=10.3389/fgene.2022.920641

ISSN=1664-8021

ABSTRACT=<p>In mammals, genomic imprinting operates <italic>via</italic> gene silencing mechanisms. Although conservation of the imprinting mechanism at the <italic>H19</italic>/<italic>IGF2</italic> 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 <italic>IGF2</italic> transcripts, age-dependent hepatic mono- to biallelic conversion, and reorganization of topologically associating domains at the porcine <italic>H19/IGF2</italic> 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 <italic>H19</italic> differentially methylated region and paternal expression of <italic>IGF2</italic>. 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 <italic>IGF2</italic> during development was analyzed. Regulatory elements in the liver were distinguished from those in the muscle where the porcine <italic>IGF2</italic> transcript was monoallelically expressed. The <italic>IGF2</italic> 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 <italic>H19</italic>/<italic>IGF2</italic> 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 <italic>H19</italic>/<italic>IGF2</italic> cluster.</p>