Genome-wide DNA Methylation Profiles of Small Intestine and Liver in Fast-growing and Slow-growing Weaning Piglets

  • Received : 2014.04.24
  • Accepted : 2014.08.15
  • Published : 2014.11.01


Although growth rate is one of the main economic traits of concern in pig production, there is limited knowledge on its epigenetic regulation, such as DNA methylation. In this study, we conducted methyl-CpG binding domain protein-enriched genome sequencing (MBD-seq) to compare genome-wide DNA methylation profile of small intestine and liver tissue between fast- and slow-growing weaning piglets. The genome-wide methylation pattern between the two different growing groups showed similar proportion of CpG (regions of DNA where a cytosine nucleotide occurs next to a guanine nucleotide in the linear sequence) coverage, genomic regions, and gene regions. Differentially methylated regions and genes were also identified for downstream analysis. In canonical pathway analysis using differentially methylated genes, pathways (triacylglycerol pathway, some cell cycle related pathways, and insulin receptor signaling pathway) expected to be related to growth rate were enriched in the two organ tissues. Differentially methylated genes were also organized in gene networks related to the cellular development, growth, and carbohydrate metabolism. Even though further study is required, the result of this study may contribute to the understanding of epigenetic regulation in pig growth.


  1. An, S., Y. Zheng, and T. Bleu. 2000. Sphingosine 1-phosphateinduced cell proliferation, survival, and related signaling events mediated by G protein-coupled receptors Edg3 and Edg5. J. Biol. Chem. 275:288-296.
  2. Andersson, L., C. S. Haley, H. Ellegren, S. A. Knott, M. Johansson, K. Andersson, L. Andersson-Eklund, I. Edfors-Lilja, M. Fredholm, and I. Hansson. 1994. Genetic mapping of quantitative trait loci for growth and fatness in pigs. Science 263:1771-1774.
  3. Andrews, S. 2010. FastQC: A quality control tool for high throughput sequence data. Reference Source. Month, Date, Year.
  4. Adada, M., D. Canals, Y. A. Hannun, and L. M. Obeid. 2013. Sphingosine-1-phosphate receptor 2. FEBS J. 280:6354-6366.
  5. Bird, A. 2002. DNA methylation patterns and epigenetic memory. Genes Dev. 16:6-21.
  6. Birney, E., J. A. Stamatoyannopoulos, A. Dutta, R. Guigo, T. R. Gingeras, E. H. Margulies, Z. Weng, M. Snyder, E. T. Dermitzakis, and R. E. Thurman. 2007. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447:799-816.
  7. Bolger, A. M., M. Lohse, and B. Usadel. 2014. Trimmomatic: A flexible trimmer for Illumina Sequence Data. Bioinformatics doi:10.1093/bioinformatics/btu170
  8. Estelle, J., F. Gil, J. Vazquez, R. Latorre, G. Ramirez, M. C. Barragan, J. M. Folch, J. L. Noguera, M. A. Toro, and M. Perez-Enciso. 2008. A quantitative trait locus genome scan for porcine muscle fiber traits reveals overdominance and epistasis. J. Anim. Sci. 86:3290-3299.
  9. Bourdon, R. and J. Brinks. 1982. Genetic, environmental and phenotypic relationships among gestation length, birth weight, growth traits and age at first calving in beef cattle. J. Anim. Sci. 55:543-553.
  10. Chavez, L., M. Lienhard, and J. Dietrich. 2013. MEDIPS: (MeD)IP-seq data analysis. R package version 1.14.0.
  11. Dolinoy, D. C. 2008. The agouti mouse model: an epigenetic biosensor for nutritional and environmental alterations on the fetal epigenome. Nutr. Rev. 66:S7-S11.
  12. Fritsche, L., C. Weigert, H.-U. Haring, and R. Lehmann. 2008. How insulin receptor substrate proteins regulate the metabolic capacity of the liver -implications for health and disease. Curr. Med. Chem. 15:1316-1329.
  13. Hazel, L. N., M. L. Baker, and C. F. Reinmiller. 1943. Genetic and environmental correlations between the growth rates of pigs at different ages. J. Anim. Sci. 2:118-128.
  14. Hu, Y., H. Xu, Z. Li, X. Zheng, X. Jia, Q. Nie, and X. Zhang. 2013. Comparison of the genome-wide DNA methylation profiles between fast-growing and slow-growing broilers. PloS one 8(2):e56411.
  15. Klose, R. J. and A. P. Bird. 2006. Genomic DNA methylation: the mark and its mediators. Trends Biochem. Sci. 31:89-97.
  16. Langmead, B. and S. L. Salzberg. 2012. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9:357-359.
  17. Li, E., C. Beard, and R. Jaenisch. 1993. Role for DNA methylation in genomic imprinting. Nature 366:362-365.
  18. Lorincz, M. C., D. R. Dickerson, M. Schmitt, and M. Groudine. 2004. Intragenic DNA methylation alters chromatin structure and elongation efficiency in mammalian cells. Nat. Struct. Mol. Biol. 11:1068-1075.
  19. Li, H., B. Handsaker, A. Wysoker, T. Fennell, J. Ruan, N. Homer, G. Marth, G. Abecasis, and R. Durbin. 2009. The sequence alignment/map format and SAMtools. Bioinformatics 25:2078-2079.
  20. Li, Q., N. Li, X. Hu, J. Li, Z. Du, L. Chen, G. Yin, J. Duan, H. Zhang, Y. Zhao, J. Wang, and N. Li. 2011. Genome-wide mapping of DNA methylation in chicken. PLoS One 6(5):e19428.
  21. Lo, L., D. McLaren, F. McKeith, R. Fernando, and J. Novakofski. 1992. Genetic analyses of growth, real-time ultrasound, carcass, and pork quality traits in Duroc and Landrace pigs: II. Heritabilities and correlations. J. Anim. Sci. 70:2387-2396.
  22. Martorell, R., C. Yarbrough, A. Lechtig, H. Delgado, and R. E. Klein. 1977. Genetic-environmental interactions in physical growth. Acta Paediatr. Scand. 66:579-584.
  23. Meyer, L. R., A. S. Zweig, A. S. Hinrichs, D. Karolchik, R. M. Kuhn, M. Wong, C. A. Sloan, K. R. Rosenbloom, G. Roe, and B. Rhead et al. 2013. The UCSC Genome Browser database: extensions and updates 2013. Nucl. Acids Res. 41:D64-D69.
  24. Mrode, R. and B. Kennedy. 1993. Genetic variation in measures of food efficiency in pigs and their genetic relationships with growth rate and backfat. Anim. Prod. 56:225-225.
  25. Pages, H. 2009. BSgenome: Infrastructure for Biostrings-based genome data packages. R package version 1.32.0
  26. Purohit, A., S. H. Tynan, R. Vallee, and S. J. Doxsey. 1999. Direct interaction of pericentrin with cytoplasmic dynein light intermediate chain contributes to mitotic spindle organization. J. Cell Biol. 147:481-492.
  27. Saltiel, A. R. and C. R. Kahn. 2001. Insulin signalling and the regulation of glucose and lipid metabolism. Nature 414:799-806.
  28. Roberts, R., V. A. Sciorra, and A. J. Morris. 1998. Human type 2 phosphatidic acid phosphohydrolases. Substrate specificity of the type 2a, 2b, and 2c enzymes and cell surface activity of the 2a isoform. J. Biol. Chem. 273:22059-22067.
  29. Rubin, C.-J., H.-J. Megens, A. M. Barrio, K. Maqbool, S. Sayyab, D. Schwochow, C. Wang, O . Carlborg, P. Jern, and C. B. Jorgensen et al. 2012. Strong signatures of selection in the domestic pig genome. Proc. Natl. Acad. Sci. 109:19529-19536.
  30. Salmon-Divon, M., H. Dvinge, K. Tammoja, and P. Bertone. 2010. PeakAnalyzer: genome-wide annotation of chromatin binding and modification loci. BMC Bioinformatics 11:415.
  31. Siegfried, Z., S. Eden, M. Mendelsohn, X. Feng, B.-Z. Tsuberi, and H. Cedar. 1999. DNA methylation represses transcription in vivo. Nat. Genet. 22:203-206.
  32. Sleeman, M. W., K. E. Wortley, K.-M. V. Lai, L. C. Gowen, J. Kintner, W. O. Kline, K. Garcia, T. N. Stitt, G. D. Yancopoulos, S. J. Wiegand, and D. J. Glass. 2005. Absence of the lipid phosphatase SHIP2 confers resistance to dietary obesity. Nat. Med. 11:199-205.
  33. Su, J., Y. Wang, X. Xing, J. Liu, and Y. Zhang. 2014. Genomewide analysis of DNA methylation in bovine placentas. BMC Genomics 15:12.
  34. Suzuki, M. M. and A. Bird. 2008. DNA methylation landscapes: Provocative insights from epigenomics. Nat. Rev. Genet. 9:465-476.
  35. The ENCODE Project Consortium. 2004. The ENCODE (ENCyclopedia of DNA elements) project. Science 306:636-640.
  36. The ENCODE Project Consortium. 2011. A user's guide to the encyclopedia of DNA elements (ENCODE). PLoS Biol. 9(4):e1001046.
  37. Trimarchi, J. M., B. Fairchild, J. Wen, and J. A. Lees. 2001. The E2F6 transcription factor is a component of the mammalian Bmi1-containing polycomb complex. Proc. Natl. Acad. Sci. 98:1519-1524.
  38. Xu, R.-J. 1996. Development of the newborn GI tract and its relation to colostrum/milk intake: A review. Reprod. Fertil. Dev. 8:35-48.

Cited by

  1. Genome-wide analysis of DNA methylation in pigs using reduced representation bisulfite sequencing vol.22, pp.5, 2015,
  2. Detection of fetal epigenetic biomarkers through genome-wide DNA methylation study for non-invasive prenatal diagnosis vol.15, pp.6, 2017,