Allele-specific aberration of imprinted domain chromosome architecture associates with large offspring syndrome
Summary: Large 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 misr...
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| Format: | Article |
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Elsevier
2022-05-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222005399 |
| _version_ | 1818186711721574400 |
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| author | Yahan Li Frimpong Boadu Max R. Highsmith Darren E. Hagen Jianlin Cheng Rocío Melissa Rivera |
| author_facet | Yahan Li Frimpong Boadu Max R. Highsmith Darren E. Hagen Jianlin Cheng Rocío Melissa Rivera |
| author_sort | Yahan Li |
| collection | DOAJ |
| description | Summary: Large 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 and IGF2R. Using bovine fetal fibroblasts, we identified CTCF binding at IGF2R imprinting 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. |
| first_indexed | 2024-12-11T22:59:29Z |
| format | Article |
| id | doaj.art-3b7b97d307c24de4b0d5b1d0ea88a640 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-11T22:59:29Z |
| publishDate | 2022-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-3b7b97d307c24de4b0d5b1d0ea88a6402022-12-22T00:47:06ZengElsevieriScience2589-00422022-05-01255104269Allele-specific aberration of imprinted domain chromosome architecture associates with large offspring syndromeYahan Li0Frimpong Boadu1Max R. Highsmith2Darren E. Hagen3Jianlin Cheng4Rocío Melissa Rivera5Division of Animal Sciences, University of Missouri, Columbia, MO 65211, USADepartment of Electrical Engineering and Computer Science, University of Missouri, Columbia, MO 65211, USADepartment of Electrical Engineering and Computer Science, University of Missouri, Columbia, MO 65211, USADepartment of Animal and Food Science, Oklahoma State University, Stillwater, OK 74078, USADepartment of Electrical Engineering and Computer Science, University of Missouri, Columbia, MO 65211, USADivision of Animal Sciences, University of Missouri, Columbia, MO 65211, USA; Corresponding authorSummary: Large 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 and IGF2R. Using bovine fetal fibroblasts, we identified CTCF binding at IGF2R imprinting 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.http://www.sciencedirect.com/science/article/pii/S2589004222005399Biological sciencesGeneticsmolecular biology |
| spellingShingle | Yahan Li Frimpong Boadu Max R. Highsmith Darren E. Hagen Jianlin Cheng Rocío Melissa Rivera Allele-specific aberration of imprinted domain chromosome architecture associates with large offspring syndrome iScience Biological sciences Genetics molecular biology |
| title | Allele-specific aberration of imprinted domain chromosome architecture associates with large offspring syndrome |
| title_full | Allele-specific aberration of imprinted domain chromosome architecture associates with large offspring syndrome |
| title_fullStr | Allele-specific aberration of imprinted domain chromosome architecture associates with large offspring syndrome |
| title_full_unstemmed | Allele-specific aberration of imprinted domain chromosome architecture associates with large offspring syndrome |
| title_short | Allele-specific aberration of imprinted domain chromosome architecture associates with large offspring syndrome |
| title_sort | allele specific aberration of imprinted domain chromosome architecture associates with large offspring syndrome |
| topic | Biological sciences Genetics molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222005399 |
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