文章基本信息

标题：Allele-specific aberration of imprinted domain chromosome architecture associates with large offspring syndrome
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作者：Yahan Li ; Frimpong Boadu ; Max R. Highsmith 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：5
页码：1-26
DOI：10.1016/j.isci.2022.104269
语种：English
出版社：Elsevier
摘要：SummaryLarge offspring syndrome (LOS) and Beckwith-Wiedemann syndrome are similar epigenetic congenital overgrowth conditions in ruminants and humans, respectively. We have reported global loss-of-imprinting, methylome epimutations, and gene misregulation in LOS. However, less than 4% of gene misregulation can be explained with short range (<20kb) alterations in DNA methylation. Therefore, we hypothesized that methylome epimutations in LOS affect chromosome architecture which results in misregulation of genes located at distances >20kb in cis and in trans (other chromosomes). Our analyses focused on two imprinted domains that frequently reveal misregulation in these syndromes, namely KvDMR1 andIGF2R. Using bovine fetal fibroblasts, we identified CTCF binding atIGF2Rimprinting control region but not KvDMR1, and allele-specific chromosome architecture of these domains in controls. In LOS, analyses identified erroneous long-range contacts and clustering tendency in the direction of expression of misregulated genes. In conclusion, altered chromosome architecture is associated with LOS.Graphical abstractDisplay OmittedHighlights•IGF2Rimprinted domain has allele-specific chromosome architecture in bovines•In bovines, CTCF binds atIGF2Rimprinting control region but not at KvDMR1•Bovine large offspring syndrome (LOS) shows altered chromosome architecture atIGF2R•Misregulated genes in LOS exhibit genomic location-based clustering tendencyBiological sciences; Genetics; Molecular biology