Whole-Genome Methylation Analysis Reveals Epigenetic Variation in Cloned and Donor Pigs

Overview

Journal Front Genet

Date 2020 Mar 11

PMID 32153632

Citations 11

Authors

Mengfen Wang

Shuaifei Feng

Guanjun Ma

Yiliang Miao

Bo Zuo

Jinxue Ruan

Shuhong Zhao

Haiyan Wang

Xiaoyong Du

Xiangdong Liu

Affiliations

Soon will be listed here.

Abstract

Somatic cloning has had a significant impact on the life sciences and is important in a variety of processes, including medical research and animal production. However, the application of somatic cloning has been limited due to its low success rate. Therefore, potential epigenetic variations between cloned and donor animals are still unclear. DNA methylation, one of the factors which is responsible for phenotypic differences in animals, is a commonly researched topic in epigenetic studies of mammals. To investigate the epigenetic variations between cloned and donor animals, we selected blood and ear fibroblasts of a donor pig and a cloned pig to perform whole-genome bisulfite sequencing (WGBS). A total of 215 and 707 differential methylation genes (DMGs) were identified in blood and ear fibroblasts, respectively. Functional annotation revealed that DMGs are enriched in many pathways, including T/B or natural killer (NK) cell differentiation, oocyte maturation, embryonic development, and reproductive hormone secretion. Moreover, 22 DMGs in the blood and 75 in the ear were associated with immune responses (e.g., , , , , , and ). We also found that 18 DMGs in blood and 53 in ear fibroblasts were involved in reproduction. Understanding the expression patterns of DMGs, especially in relation to immune responses and reproduction, will reveal insights that will aid the advancement of future somatic cloning techniques in swine.

Citing Articles

Reliable Polymerase Chain Reaction Methods for Screening for Porcine Endogenous Retroviruses-C (PERV-C) in Pigs.

Jhelum H, Kunec D, Papatsiros V, Kaufer B, Denner J Viruses. 2025; 17(2).

PMID: 40006919 PMC: 11860680. DOI: 10.3390/v17020164.

Extensive differential DNA methylation between tuberculosis skin test positive and skin test negative cattle.

Bhat S, Parveen A, Gormley E, Meade K BMC Genomics. 2024; 25(1):762.

PMID: 39107682 PMC: 11301934. DOI: 10.1186/s12864-024-10574-x.

Kidney xenotransplantation edges closer to the clinic.

Wolf E, Reichart B Nat Rev Nephrol. 2023; 20(4):204-205.

PMID: 37973840 DOI: 10.1038/s41581-023-00790-1.

Epigenetic biomarkers for animal welfare monitoring.

Whelan R, Tonges S, Bohl F, Lyko F Front Vet Sci. 2023; 9:1107843.

PMID: 36713882 PMC: 9874107. DOI: 10.3389/fvets.2022.1107843.

Comparison of genome-wide DNA methylation patterns between antler precartilage and cartilage.

Wu J, Yang F, Wu X, Liu X, Zheng D Mol Genet Genomics. 2022; 298(2):343-352.

PMID: 36513842 DOI: 10.1007/s00438-022-01983-2.

References

Kaur G, Trowsdale J, Fugger L . Natural killer cells and their receptors in multiple sclerosis. Brain. 2012; 136(Pt 9):2657-76. PMC: 3754456. DOI: 10.1093/brain/aws159. View

Jones P, Takai D . The role of DNA methylation in mammalian epigenetics. Science. 2001; 293(5532):1068-70. DOI: 10.1126/science.1063852. View

Rideout 3rd W, Eggan K, Jaenisch R . Nuclear cloning and epigenetic reprogramming of the genome. Science. 2001; 293(5532):1093-8. DOI: 10.1126/science.1063206. View

Shibata M, Otake M, Tsuchiya S, Chikyu M, Horiuchi A, Kawarasaki T . Reproductive and growth performance in Jin Hua pigs cloned from somatic cell nuclei and the meat quality of their offspring. J Reprod Dev. 2006; 52(5):583-90. DOI: 10.1262/jrd.18004. View

Pacheco Y, McLean A, Rohrbach J, Porichis F, Kaufmann D, Kavanagh D . Simultaneous TCR and CD244 signals induce dynamic downmodulation of CD244 on human antiviral T cells. J Immunol. 2013; 191(5):2072-81. PMC: 3777852. DOI: 10.4049/jimmunol.1300435. View

Auclair G, Weber M . Mechanisms of DNA methylation and demethylation in mammals. Biochimie. 2012; 94(11):2202-11. DOI: 10.1016/j.biochi.2012.05.016. View

Clarkson N, Brown M . Inhibition and activation by CD244 depends on CD2 and phospholipase C-gamma1. J Biol Chem. 2009; 284(37):24725-34. PMC: 2757176. DOI: 10.1074/jbc.M109.028209. View

Kuroda Y, Kaneko S, Yoshimura Y, Nozawa S, Mikoshiba K . Are there inositol 1,4,5-triphosphate (IP3) receptors in human sperm?. Life Sci. 1999; 65(2):135-43. DOI: 10.1016/s0024-3205(99)00230-1. View

Glanzner W, Wachter A, Coutinho A, Albornoz M, Duggavathi R, Goncalves P . Altered expression of BRG1 and histone demethylases, and aberrant H3K4 methylation in less developmentally competent embryos at the time of embryonic genome activation. Mol Reprod Dev. 2016; 84(1):19-29. DOI: 10.1002/mrd.22762. View

10.

Tellez Freitas C, Johnson D, Weber K . T Cell Calcium Signaling Regulation by the Co-Receptor CD5. Int J Mol Sci. 2018; 19(5). PMC: 5983667. DOI: 10.3390/ijms19051295. View

11.

Symoens S, Barnes A, Gistelinck C, Malfait F, Guillemyn B, Steyaert W . Genetic Defects in TAPT1 Disrupt Ciliogenesis and Cause a Complex Lethal Osteochondrodysplasia. Am J Hum Genet. 2015; 97(4):521-34. PMC: 4596895. DOI: 10.1016/j.ajhg.2015.08.009. View

12.

Sun B, Boxer L, Ransohoff J, Siprashvili Z, Qu K, Lopez-Pajares V . CALML5 is a ZNF750- and TINCR-induced protein that binds stratifin to regulate epidermal differentiation. Genes Dev. 2015; 29(21):2225-30. PMC: 4647556. DOI: 10.1101/gad.267708.115. View

13.

Mazzone R, Zwergel C, Artico M, Taurone S, Ralli M, Greco A . The emerging role of epigenetics in human autoimmune disorders. Clin Epigenetics. 2019; 11(1):34. PMC: 6390373. DOI: 10.1186/s13148-019-0632-2. View

14.

Wang Y, Yu X, Liu Y, Li X, Liu X, Wang P . Reduced nucleic acid methylation impairs meiotic maturation and developmental potency of pig oocytes. Theriogenology. 2018; 121:160-167. DOI: 10.1016/j.theriogenology.2018.08.009. View

15.

Kollmann K, Heller G, Schneckenleithner C, Warsch W, Scheicher R, Ott R . A Kinase-Independent Function of CDK6 Links the Cell Cycle to Tumor Angiogenesis. Cancer Cell. 2016; 30(2):359-360. PMC: 5637299. DOI: 10.1016/j.ccell.2016.07.003. View

16.

Uras I, Scheicher R, Kollmann K, Glosmann M, Prchal-Murphy M, Tigan A . Cdk6 contributes to cytoskeletal stability in erythroid cells. Haematologica. 2017; 102(6):995-1005. PMC: 5451331. DOI: 10.3324/haematol.2016.159947. View

17.

Akagi S, Matsukawa K, Takahashi S . Factors affecting the development of somatic cell nuclear transfer embryos in Cattle. J Reprod Dev. 2014; 60(5):329-35. PMC: 4219988. DOI: 10.1262/jrd.2014-057. View

18.

Adachi N, Yamaguchi D, Watanabe A, Miura N, Sunaga S, Oishi H . Growth, reproductive performance, carcass characteristics and meat quality in F1 and F2 progenies of somatic cell-cloned pigs. J Reprod Dev. 2014; 60(2):100-5. PMC: 3999388. DOI: 10.1262/jrd.2012-167. View

19.

Wang Y, Zhong H, Xie X, Chen C, Huang D, Shen L . Long noncoding RNA derived from CD244 signaling epigenetically controls CD8+ T-cell immune responses in tuberculosis infection. Proc Natl Acad Sci U S A. 2015; 112(29):E3883-92. PMC: 4517270. DOI: 10.1073/pnas.1501662112. View

20.

Yuan X, Gao N, Xing Y, Zhang H, Zhang A, Liu J . Profiling the genome-wide DNA methylation pattern of porcine ovaries using reduced representation bisulfite sequencing. Sci Rep. 2016; 6:22138. PMC: 4766444. DOI: 10.1038/srep22138. View