Abstract
Genomic imprinting is an epigenetic regulation mechanism in mammals resulting in the parentally dependent monoallelic expression of genes. Imprinting disorders in humans are associated with several congenital syndromes and cancers and remain the focus of many medical studies. Cattle is a better model organism for investigating human embryo development than mice. Imprinted genes usually cluster on chromosomes and are regulated by different methylation regions (DMRs) located in imprinting control regions that control gene expression in cis. There is an imprinted locus on human chromosome 16q24.1 associated with congenital lethal developmental lung disease in newborns. However, genomic imprinting on bovine chromosome 18, which is homologous with human chromosome 16 has not been systematically studied. The aim of this study was to analyze the allelic expressions of eight genes (CDH13, ATP2C2, TLDC1, COTL1, CRISPLD2, ZDHHC7, KIAA0513, and GSE1) on bovine chromosome 18 and to search the DMRs associated gene allelic expression. Three transcript variants of the ZDHHC7 gene (X1, X2, and X5) showed maternal imprinting in bovine placentas. In addition, the monoallelic expression of X2 and X5 was tissue-specific. Five transcripts of the KIAA0513 gene showed tissue- and isoform-specific monoallelic expression. The CDH13, ATP2C2, and TLDC1 genes exhibited tissue-specific imprinting, however, COTL1, CRISLPLD2, and GSE1 escaped imprinting. Four DMRs, established after fertilization, were found in this region. Two DMRs were located between the ZDHHC7 and KIAA0513 genes, and two were in exon 1 of the CDH13 and ATP2C2 genes, respectively. The results from this study support future studies on the molecular mechanism to regulate the imprinting of candidate genes on bovine chromosome 18.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data availability
The data used to support the findings of this study are included within the article, and the data are available from the corresponding author upon request.
Abbreviations
- BSP:
-
Bisulfite polymerase chain reaction
- DMR:
-
Different methylation region
- gDMR:
-
Germline different methylation region
- ICR:
-
Imprinting control regions
- PCR:
-
Polymerase chain reaction
- RT-PCR:
-
Reverse transcription polymerase chain reaction
- sDMR:
-
Somatic different methylation region
References
Abril-Fornaguera J, Torrens L, Andreu-Oller C et al (2023) Identification of IGF2 as genomic driver and actionable therapeutic target in hepatoblastoma. Mol Cancer Ther 22(4):485–498. https://doi.org/10.1158/1535-7163
Babak T, DeVeale B, Tsang EK et al (2015) Genetic conflict reflected in tissue-specific maps of genomic imprinting in human and mouse. Nat Genet 47(5):544–549. https://doi.org/10.1038/ng.3274
Baran Y, Subramaniam M, Biton A et al (2015) The landscape of genomic imprinting across diverse adult human tissues. Genome Res 25(7):927–936. https://doi.org/10.1101/gr.192278.115
Barlow DP, Bartolomei MS (2014) Genomic imprinting in mammals. Cold Spring Harb Perspect Biol 6(2):a018382. https://doi.org/10.1101/cshperspect.a018382
Bartolomei MS, Ferguson-Smith AC (2011) Mammalian genomic imprinting. Cold Spring Harb Perspect Biol 3(7):a002592. https://doi.org/10.1101/cshperspect.a002592
Bourneuf E, Otz P, Pausch H et al (2017) Rapid discovery of De Novo deleterious mutations in cattle enhances the value of livestock as model species. Sci Rep 7(1):11466. https://doi.org/10.1038/s41598-017-11523-3
Brideau CM, Eilertson KE, Hagarman JA et al (2010) Successful computational prediction of novel imprinted genes from epigenomic features. Mol Cell Biol 30(13):3357–3370. https://doi.org/10.1128/MCB.01355-09
Chen Z, Hagen DE, Wang J et al (2016) Global assessment of imprinted gene expression in the bovine conceptus by next generation sequencing. Epigenetics 11(7):501–516. https://doi.org/10.1080/15592294.2016.1184805
Dong Y, Jin L, Liu X et al (2022) IMPACT and OSBPL1A are two isoform-specific imprinted genes in bovines. Theriogenology 184:100–109. https://doi.org/10.1016/j.theriogenology.2022.02.023
Eggermann T, Curtis M, Zerres K et al (2004) Maternal uniparental disomy 16 and genetic counseling: new case and survey of published cases. Genet Couns 15(2):183–190
Eggermann T, Perez de Nanclares G, Maher ER et al (2015) Imprinting disorders: a group of congenital disorders with overlapping patterns of molecular changes affecting imprinted loci. Clin Epigenetics 7:123. https://doi.org/10.1186/s13148-015-0143-8
Ferguson-Smith AC, Cattanach BM, Barton SC et al (1991) Embryological and molecular investigations of parental imprinting on mouse chromosome 7. Nature 351(6328):667–670. https://doi.org/10.1038/351667a0
Ferguson-Smith AC (2011) Genomic imprinting: the emergence of an epigenetic paradigm]. Nat Rev Genet 12(8):565–575. https://doi.org/10.1038/nrg3032
Finelli MJ, Sanchez-Pulido L, Liu KX et al (2016) The evolutionarily conserved Tre2/Bub2/Cdc16 (TBC), Lysin Motif (LysM), domain catalytic (TLDc) domain is neuroprotective against oxidative stress. J Biol Chem 291(6):2751–2763. https://doi.org/10.1074/jbc.M115.685222
Hanna CW, Kelsey G (2014) The specification of imprints in mammals. Heredity (edinb) 113(2):176–183. https://doi.org/10.1038/hdy.2014.54
Hansen PJ (2014) Current and future assisted reproductive technologies for mammalian farm animals. Adv Exper Med Biol 752:1–22. https://doi.org/10.1007/978-1-4614-8887-3_1
Hiver S, Shimizu-Mizuno N, Ikawa Y et al (2023) Gse1, a component of the CoREST complex, is required for placenta development in the mouse. Dev Biol 498:97–105. https://doi.org/10.1016/j.ydbio.2023.03.009
Jadhav B, Monajemi R, Gagalova KK et al (2019) RNA-Seq in 296 phased trios provides a high-resolution map of genomic imprinting. BMC Biol 17(1):50. https://doi.org/10.1186/s12915-019-0674-0
John RM, Surani MA (1996) Imprinted genes and regulation of gene expression by epigenetic inheritance. Curr Opin Cell Biol 8(3):348–353. https://doi.org/10.1016/s0955-0674(96)80008-1
Joshi RS, Garg P, Zaitlen N et al (2016) DNA methylation profiling of uniparental disomy subjects provides a map of parental epigenetic bias in the human genome. Am J Hum Genet 99(3):555–566. https://doi.org/10.1016/j.ajhg.2016.06.032
Kerkenberg N, Wachsmuth L, Zhang M et al (2021) Brain microstructural changes in mice persist in adulthood and are modulated by the palmitoyl acyltransferase ZDHHC7. Eur J Neurosci 54(6):5951–5967. https://doi.org/10.1111/ejn.15415
Kim JY, Jelinek J, Lee YH et al (2023) Hypomethylation in MTNR1B: a novel epigenetic marker for atherosclerosis profiling using stenosis radiophenotype and blood inflammatory cells. Clin Epigenetics 15(1):11. https://doi.org/10.1186/s13148-023-01423-x
Koerner MV, Pauler FM, Huang R et al (2009) The function of non-coding RNAs in genomic imprinting. Development 136(11):1771–1783. https://doi.org/10.1242/dev.030403
Lauriat TL, Dracheva S, Kremerskothen J et al (2006) Characterization of KIAA0513, a novel signaling molecule that interacts with modulators of neuroplasticity, apoptosis, and the cytoskeleton. Brain Res 1121(1):1–11. https://doi.org/10.1016/j.brainres.2006.08.099
Luedi PP, Dietrich FS, Weidman JR, Bosko JM, Jirtle RL, Hartemink AJ (2007) Computational and experimental identification of novel human imprinted genes. Genome Res 17(12):1723–1730. https://doi.org/10.1101/gr.6584707
Macartney-Coxson D, Benton MC, Blick R et al (2017) Genome-wide DNA methylation analysis reveals loci that distinguish different types of adipose tissue in obese individuals. Clin Epigenetics 9:48. https://doi.org/10.1186/s13148-017-0344-4
Morison IM, Paton CJ, Cleverley SD (2001) The imprinted gene and parent-of-origin effect database. Nucleic Acids Res 29(1):275–276. https://doi.org/10.1093/nar/29.1.275
Mozaffari SV, Stein MM, Magnaye KM et al (2018) Parent of origin gene expression in a founder population identifies two new candidate imprinted genes at known imprinted regions. PLoS ONE 13(9):e0203906. https://doi.org/10.1371/journal.pone.0203906
Pilvar D, Reiman M, Pilvar A et al (2019) Parent-of-origin-specific allelic expression in the human placenta is limited to established imprinted loci and it is stably maintained across pregnancy. Clin Epigenetics 11(1):94. https://doi.org/10.1186/s13148-019-0692-3
Sanchez-Delgado M, Court F, Vidal E et al (2016) Human oocyte-derived methylation differences persist in the placenta revealing widespread transient imprinting. PLoS Genet 12(11):e1006427. https://doi.org/10.1371/journal.pgen.1006427
Santoni FA, Stamoulis G, Garieri M et al (2017) Detection of imprinted genes by single-cell allele-specific gene expression. Am J Hum Genet 100(3):444–453. https://doi.org/10.1016/j.ajhg.2017.01.028
Scheuvens R, Begemann M, Soellner L et al (2017) Maternal uniparental disomy of chromosome 16 [upd(16)mat]: clinical features are rather caused by (hidden) trisomy 16 mosaicism than by upd(16)mat itself. Clin Genet 92(1):45–51. https://doi.org/10.1111/cge.12958
Schulze KV, Szafranski P, Lesmana H et al (2019) Novel parent-of-origin-specific differentially methylated loci on chromosome 16. Clin Epigenetics 11(1):60. https://doi.org/10.1186/s13148-019-0655-8
Shao Y, Li W, Zhang L et al (2022) CDH13 is a prognostic biomarker and a potential therapeutic target for patients with clear cell renal cell carcinoma. Am J Cancer Res 12(10):4520–4544
Soellner L, Begemann M, Mackay DJ et al (2017) Recent advances in imprinting disorders. Clin Genet 91(1):3–13. https://doi.org/10.1111/cge.12827
Stelzer Y, Bar S, Bartok O et al (2015) Differentiation of human parthenogenetic pluripotent stem cells reveals multiple tissue- and isoform-specific imprinted transcripts. Cell Rep 11(2):308–320. https://doi.org/10.1016/j.celrep.2015.03.023
Wan J, Li R, Zhang Y et al (2018) Pregnancy outcome of autosomal aneuploidies other than common trisomies detected by noninvasive prenatal testing in routine clinical practice. Prenat Diagn 38(11):849–857. https://doi.org/10.1002/pd.5340
Wang Y, Zhang L, Yang J et al (2018) CDH13 promoter methylation regulates cisplatin resistance of non-small cell lung cancer cells. Oncol Lett 16(5):5715–5722. https://doi.org/10.3892/ol.2018.9325
Yang J, Niu H, Huang Y et al (2016) A systematic analysis of the relationship of CDH13 promoter methylation and breast cancer risk and prognosis. PLoS ONE 11(5):e0149185. https://doi.org/10.1371/journal.pone.0149185
Zhang H, Kho AT, Wu Q et al (2016) CRISPLD2 (LGL1) inhibits proinflammatory mediators in human fetal, adult, and COPD lung fibroblasts and epithelial cells. Physiol Rep 4(17):e12942. https://doi.org/10.14814/phy2.12942
Zhu M, Jia L, Li F, Jia J (2020) Identification of KIAA0513 and other hub genes associated with alzheimer disease using weighted gene coexpression network analysis. Front Genet 11:981. https://doi.org/10.3389/fgene.2020.00981
Zink F, Magnusdottir DN, Magnusson OT et al (2018) Insights into imprinting from parent-of-origin phased methylomes and transcriptomes. Nat Genet 50(11):1542–1552. https://doi.org/10.1038/s41588-018-0232-7
Funding
This study was supported by the Hebei Province Natural Science Foundation (C2023204145 and C2022201058), the Hebei Province Agricultural Industry Technology System Innovation Team (HBCT2024240206, HBCT2024240202), the Earmarked Fund for China Agriculture Research System No (CARS36), the National Foreign Expert Project (G2022003015L), and S&T Program of Hebei (22326321D).
Author information
Authors and Affiliations
Contributions
Haonan Huo, Cui Zhang, Shujing Li, Shujie Li, Wenli Yu, designed the research. Haonan Huo, Cui Zhang, Yinjiao Zhang, Siwei Wang performed research, Haonan Huo, Cui Zhang, Weina Chen, Kun Wang,Siwei Wang contributed analytical/computational tools, Haonan Huo, Shijie Li, Shujing Li, wrote the paper. All authors read, discussed, and approved the fnal version of the manuscript.
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare no conflict of interest.
Ethical approval
Ethical approval for the use of bovine somatic tissues including placenta samples was granted by the Animal Protection Committee of Agricultural Research at Hebei Agricultural University. All animal experiments were approved by the Animal Care Committee of Agricultural Research at Hebei Agricultural University (No. 14021).
Additional information
Communicated by Joan Cerdá.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Huo, H., Zhang, C., Wang, K. et al. A novel imprinted locus on bovine chromosome 18 homologous with human chromosome 16q24.1. Mol Genet Genomics 299, 40 (2024). https://doi.org/10.1007/s00438-024-02123-8
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s00438-024-02123-8