Genome-Wide Analysis of DNA Methylation before- and after Exercise in the Thoroughbred Horse with MeDIP-Seq

  • Gim, Jeong-An (Department of Biological Sciences, College of Natural Sciences, Pusan National University) ;
  • Hong, Chang Pyo (TBI, Theragen BiO Institute, TheragenEtex) ;
  • Kim, Dae-Soo (Genome Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Moon, Jae-Woo (TBI, Theragen BiO Institute, TheragenEtex) ;
  • Choi, Yuri (Department of Biological Sciences, College of Natural Sciences, Pusan National University) ;
  • Eo, Jungwoo (Department of Biological Sciences, College of Natural Sciences, Pusan National University) ;
  • Kwon, Yun-Jeong (Department of Biological Sciences, College of Natural Sciences, Pusan National University) ;
  • Lee, Ja-Rang (Department of Biological Sciences, College of Natural Sciences, Pusan National University) ;
  • Jung, Yi-Deun (Department of Biological Sciences, College of Natural Sciences, Pusan National University) ;
  • Bae, Jin-Han (Department of Biological Sciences, College of Natural Sciences, Pusan National University) ;
  • Choi, Bong-Hwan (Division of Animal Genomics and Bioinformatics, National Institute of Animal Science, Rural Development Administration) ;
  • Ko, Junsu (TBI, Theragen BiO Institute, TheragenEtex) ;
  • Song, Sanghoon (TBI, Theragen BiO Institute, TheragenEtex) ;
  • Ahn, Kung (TBI, Theragen BiO Institute, TheragenEtex) ;
  • Ha, Hong-Seok (Department of Genetics, Human Genetics Institute of New Jersey, Rutgers, the State University of New Jersey) ;
  • Yang, Young Mok (Department of Pathology, School of Medicine, and Institute of Biomedical Science and Technology, Konkuk University) ;
  • Lee, Hak-Kyo (Department of Biotechnology, Hankyong National University) ;
  • Park, Kyung-Do (Department of Biotechnology, Hankyong National University) ;
  • Do, Kyoung-Tag (Department of Equine Sciences, Sorabol College) ;
  • Han, Kyudong (Department of Nanobiomedical Science and WCU Research Center, Dankook University) ;
  • Yi, Joo Mi (Research Center, Dongnam Institute of Radiological and Medical Science (DIRAMS)) ;
  • Cha, Hee-Jae (Department of Parasitology and Genetics, Kosin University College of Medicine) ;
  • Ayarpadikannan, Selvam (Department of Biological Sciences, College of Natural Sciences, Pusan National University) ;
  • Cho, Byung-Wook (Department of Animal Science, College of Life Sciences, Pusan National University) ;
  • Bhak, Jong (TBI, Theragen BiO Institute, TheragenEtex) ;
  • Kim, Heui-Soo (Department of Biological Sciences, College of Natural Sciences, Pusan National University)
  • Received : 2014.05.26
  • Accepted : 2014.11.21
  • Published : 2015.03.31


Athletic performance is an important criteria used for the selection of superior horses. However, little is known about exercise-related epigenetic processes in the horse. DNA methylation is a key mechanism for regulating gene expression in response to environmental changes. We carried out comparative genomic analysis of genome-wide DNA methylation profiles in the blood samples of two different thoroughbred horses before and after exercise by methylated-DNA immunoprecipitation sequencing (MeDIP-Seq). Differentially methylated regions (DMRs) in the pre-and post-exercise blood samples of superior and inferior horses were identified. Exercise altered the methylation patterns. After 30 min of exercise, 596 genes were hypomethy-lated and 715 genes were hypermethylated in the superior horse, whereas in the inferior horse, 868 genes were hypomethylated and 794 genes were hypermethylated. These genes were analyzed based on gene ontology (GO) annotations and the exercise-related pathway patterns in the two horses were compared. After exercise, gene regions related to cell division and adhesion were hypermethylated in the superior horse, whereas regions related to cell signaling and transport were hypermethylated in the inferior horse. Analysis of the distribution of methylated CpG islands confirmed the hypomethylation in the gene-body methylation regions after exercise. The methylation patterns of transposable elements also changed after exercise. Long interspersed nuclear elements (LINEs) showed abundance of DMRs. Collectively, our results serve as a basis to study exercise-based reprogramming of epigenetic traits.


DNA methylation;exercise;MeDIP-Seq;thoroughbred horse;transposable elements


  1. Handschin, C., Kobayashi, Y.M., Chin, S., Seale, P., Campbell, K.P., and Spiegelman, B.M. (2007b). PGC-1alpha regulates the neuromuscular junction program and ameliorates Duchenne muscular dystrophy. Genes Dev. 21, 770-783.
  2. Hill, E.W., Gu, J., Eivers, S.S., Fonseca, R.G., McGivney, B.A., Govindarajan, P., Orr, N., Katz, L.M., and MacHugh, D.E. (2010a). A sequence polymorphism in MSTN predicts sprinting ability and racing stamina in thoroughbred horses. PLoS One 5, e8645.
  3. Hill, E.W., Gu, J., McGivney, B.A., and MacHugh, D.E. (2010b). Targets of selection in the Thoroughbred genome contain exercise-relevant gene SNPs associated with elite racecourse performance. Anim. Genet. 41 Suppl 2, 56-63.
  4. Hsiung, D.T., Marsit, C.J., Houseman, E.A., Eddy, K., Furniss, C.S., McClean, M.D., and Kelsey, K.T. (2007). Global DNA methylation level in whole blood as a biomarker in head and neck squamous cell carcinoma. Cancer Epidemiol. Biomarkers Prev. 16, 108-114.
  5. Hu, Y., Xu, H., Li, Z., Zheng, X., Jia, X., Nie, Q., and Zhang, X. (2013). Comparison of the genome-wide DNA methylation profiles between fast-growing and slow-growing broilers. PLoS One 8, e56411.
  6. Huang da, W., Sherman, B.T., and Lempicki, R.A. (2009). Sys-tematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc. 4, 44-57
  7. Griffin, M., Casadio, R., and Bergamini, C.M. (2002). Transglutaminases: nature's biological glues. Biochem. J. 368, 377-396.
  8. Handschin, C., Chin, S., Li, P., Liu, F., Maratos-Flier, E., Lebrasseur, N.K., Yan, Z., and Spiegelman, B.M. (2007a). Skeletal muscle fiber-type switching, exercise intolerance, and myopathy in PGC-1alpha muscle-specific knock-out animals. J. Biol. Chem. 282, 30014-30021.
  9. Jaenisch, R., and Bird, A. (2003). Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat. Genet. 33 Suppl, 245-254.
  10. El-Maarri, O., Walier, M., Behne, F., van Uum, J., Singer, H., Diaz-Lacava, A., Nusgen, N., Niemann, B., Watzka, M., Reinsberg, J., et al. (2011). Methylation at global LINE-1 repeats in human blood are affected by gender but not by age or natural hormone cycles. PLoS One 6, e16252.
  11. Farmer, J., Zhao, X., van Praag, H., Wodtke, K., Gage, F.H., and Christie, B.R. (2004). Effects of voluntary exercise on synaptic plasticity and gene expression in the dentate gyrus of adult male Sprague-Dawley rats in vivo. Neuroscience 124, 71-79
  12. Feber, A., Wilson, G.A., Zhang, L., Presneau, N., Idowu, B., Down, T.A., Rakyan, V.K., Noon, L.A., Lloyd, A.C., Stupka, E., et al. (2011). Comparative methylome analysis of benign and malignant peripheral nerve sheath tumors. Genome Res. 21, 515-524.
  13. Gano, L.B., Donato, A.J., Pierce, G.L., Pasha, H.M., Magerko, K.A., Roeca, C., and Seals, D.R. (2011). Increased proinflammatory and oxidant gene expression in circulating mononuclear cells in older adults: amelioration by habitual exercise. Physiol. Genomics 43, 895-902.
  14. Gao, L., Geng, Y., Li, B., Chen, J., and Yang, J. (2010). Genomewide DNA methylation alterations of Alternanthera philoxeroides in natural and manipulated habitats: implications for epigenetic regulation of rapid responses to environmental fluctuation and phenotypic variation. Plant Cell Environ. 33, 1820-1827
  15. Garcia-Lopez, D., Hakkinen, K., Cuevas, M.J., Lima, E., Kauhanen, A., Mattila, M., Sillanpaa, E., Ahtiainen, J.P., Karavirta, L., Almar, M., et al. (2007). Effects of strength and endurance training on antioxidant enzyme gene expression and activity in middle-aged men. Scand. J. Med. Sci. Sports 17, 595-604.
  16. Gardiner, P., Dai, Y., and Heckman, C.J. (2006). Effects of exercise training on alpha-motoneurons. J. Appl. Physiol. 101, 1228-1236.
  17. Gim, J.A., Ayarpadikannan, S., Eo, J., Kwon, Y.J., Choi, Y., Lee, H.K., Park, K.D., Yang, Y.M., Cho, B.W., and Kim, H.S. (2014). Transcriptional expression changes of glucose metabolism genes after exercise in thoroughbred horses. Gene 547, 152-158
  18. Girardot, M., Guibert, S., Laforet, M.P., Gallard, Y., Larroque, H., and Oulmouden, A. (2006). The insertion of a full-length Bos taurus LINE element is responsible for a transcriptional deregulation of the Normande Agouti gene. Pigment Cell Res. 19, 346-355.
  19. Goeppert, B., Konermann, C., Schmidt, C.R., Bogatyrova, O., Geiselhart, L., Ernst, C., Gu, L., Becker, N., Zucknick, M., Mehrabi, A., et al. (2014). Global alterations of DNA methylation in cholangiocarcinoma target the Wnt signaling pathway. Hepatology 59, 544-554.
  20. Gomez-Pinilla, F., Zhuang, Y., Feng, J., Ying, Z., and Fan, G. (2011). Exercise impacts brain-derived neurotrophic factor plasticity by engaging mechanisms of epigenetic regulation. Eur. J. Neurosci. 33, 383-390.
  21. Goto, M., Terada, S., Kato, M., Katoh, M., Yokozeki, T., Tabata, I., and Shimokawa, T. (2000). cDNA Cloning and mRNA analysis of PGC-1 in epitrochlearis muscle in swimming-exercised rats. Biochem. Biophys. Res. Commun. 274, 350-354.
  22. Chang, S.C., Tucker, T., Thorogood, N.P., and Brown, C.J. (2006). Mechanisms of X-chromosome inactivation. Front. Biosci. 11, 852-866.
  23. Chavez, L., Jozefczuk, J., Grimm, C., Dietrich, J., Timmermann, B., Lehrach, H., Herwig, R., and Adjaye, J. (2010). Computational analysis of genome-wide DNA methylation during the differentiation of human embryonic stem cells along the endodermal lineage. Genome Res. 20, 1441-1450.
  24. Clausen, T. (2008). Role of Na+,K+-pumps and transmembrane $Na^+$, $K^+$-distribution in muscle function. The FEPS lecture-Bratislava 2007. Acta Physiol. 192, 339-349
  25. Cywinska, A., Szarska, E., Kowalska, A., Ostaszewski, P., and Schollen-berger, A. (2011). Gender differences in exercise--induced intra-vascular haemolysis during race training in thoroughbred horses. Res. Vet. Sci. 90, 133-137
  26. Dauksa, A., Gulbinas, A., Barauskas, G., Pundzius, J., Oldenburg, J., and El-Maarri, O. (2012). Whole blood DNA aberrant methylation in pancreatic adenocarcinoma shows association with the course of the disease: a pilot study. PLoS One 7, e37509
  27. Dawson, M.A., and Kouzarides, T. (2012). Cancer epigenetics: from mechanism to therapy. Cell 150, 12-27
  28. Dejana, E., Orsenigo, F., and Lampugnani, M.G. (2008). The role of adherens junctions and VE-cadherin in the control of vascular permeability. J. Cell Sci. 121, 2115-2122.
  29. Dempsey, J.A., and Wagner, P.D. (1999). Exercise-induced arterial hypoxemia. J. Appl. Physiol. 87, 1997-2006.
  30. Dietrich, M.O., Mantese, C.E., Porciuncula, L.O., Ghisleni, G., Vinade, L., Souza, D.O., and Portela, L.V. (2005). Exercise affects glutamate receptors in postsynaptic densities from cortical mice brain. Brain Res. 1065, 20-25.
  31. Eivers, S.S., McGivney, B.A., Fonseca, R.G., MacHugh, D.E., Menson, K., Park, S.D., Rivero, J.L., Taylor, C.T., Katz, L.M., and Hill, E.W. (2010). Alterations in oxidative gene expression in equine skeletal muscle following exercise and training. Physiol. Genomics 40, 83-93.
  32. Eivers, S.S., McGivney, B.A., Gu, J., MacHugh, D.E., Katz, L.M., and Hill, E.W. (2012). PGC-1alpha encoded by the PPARGC1A gene regulates oxidative energy metabolism in equine skeletal muscle during exercise. Anim. Genet. 43, 153-162.
  33. El-Maarri, O., Becker, T., Junen, J., Manzoor, S.S., Diaz-Lacava, A., Schwaab, R., Wienker, T., and Oldenburg, J. (2007). Gender specific differences in levels of DNA methylation at selected loci from human total blood: a tendency toward higher methylation levels in males. Hum. Genet. 122, 505-514.
  34. Carlsson, L., Yu, J.G., and Thornell, L.E. (2008). New aspects of obscurin in human striated muscles. Histochem. Cell Biol. 130, 91-103.
  35. Carnell, A.N., and Goodman, J.I. (2003). The long (LINEs) and the short (SINEs) of it: altered methylation as a precursor to toxicity. Toxicol. Sci. 75, 229-235.
  36. Al-Moundhri, M.S., Al-Nabhani, M., Tarantini, L., Baccarelli, A., and Rusiecki, J.A. (2010). The prognostic significance of whole blood global and specific DNA methylation levels in gastric adenocarcinoma. PLoS One 5, e15585.
  37. Allen, D.G., Lamb, G.D., and Westerblad, H. (2008). Impaired calcium release during fatigue. J. Appl. Physiol. 104, 296-305.
  38. Ball, M.P., Li, J.B., Gao, Y., Lee, J.H., LeProust, E.M., Park, I.H., Xie, B., Daley, G.Q., and Church, G.M. (2009). Targeted and genomescale strategies reveal gene-body methylation signatures in human cells. Nat. Biotechnol. 27, 361-368
  39. Barres, R., Yan, J., Egan, B., Treebak, J.T., Rasmussen, M., Fritz, T., Caidahl, K., Krook, A., O'Gorman, D.J., and Zierath, J.R. (2012). Acute exercise remodels promoter methylation in human skeletal muscle. Cell Metab. 15, 405-411.
  40. Bird, A. (2002). DNA methylation patterns and epigenetic memory. Genes Dev. 16, 6-21.
  41. Bosviel, R., Garcia, S., Lavediaux, G., Michard, E., Dravers, M., Kwiatkowski, F., Bignon, Y.J., and Bernard-Gallon, D.J. (2012). BRCA1 promoter methylation in peripheral blood DNA was identified in sporadic breast cancer and controls. Cancer Epidemiol. 36, e177-182.
  42. Burgomaster, K.A., Howarth, K.R., Phillips, S.M., Rakobowchuk, M., Macdonald, M.J., McGee, S.L., and Gibala, M.J. (2008). Similar metabolic adaptations during exercise after low volume sprint interval and traditional endurance training in humans. J. Physiol. 586, 151-160.
  43. Capomaccio, S., Verini-Supplizi, A., Galla, G., Vitulo, N., Barcaccia, G., Felicetti, M., Silvestrelli, M., and Cappelli, K. (2010). Transcription of LINE-derived sequences in exercise-induced stress in horses. Anim. Genet. 41 Suppl 2, 23-27
  44. Jair, K.W., Bachman, K.E., Suzuki, H., Ting, A.H., Rhee, I., Yen, R.W., Baylin, S.B., and Schuebel, K.E. (2006). De novo CpG island methylation in human cancer cells. Cancer Res. 66, 682-692.
  45. Jemiolo, B., and Trappe, S. (2004). Single muscle fiber gene expression in human skeletal muscle: validation of internal control with exercise. Biochem. Biophys. Res. Commun. 320, 1043-1050.
  46. Kim, H., Lee, T., Park, W., Lee, J.W., Kim, J., Lee, B.Y., Ahn, H., Moon, S., Cho, S., Do, K.T., et al. (2013a). Peeling back the evolutionary layers of molecular mechanisms responsive to exercise-stress in the skeletal muscle of the racing horse. DNA Res. 20, 287-298
  47. Kim, Y.J., Park, S.W., Kim, T.H., Park, J.S., Cheong, H.S., Shin, H.D., and Park, C.S. (2013b). Genome-wide methylation profiling of the bronchial mucosa of asthmatics: relationship to atopy. BMC Med. Genet. 14, 39
  48. Klose, R.J., and Bird, A.P. (2006). Genomic DNA methylation: the mark and its mediators. Trends Biochem. Sci. 31, 89-97
  49. Laird, P.W. (2010). Principles and challenges of genomewide DNA methylation analysis. Nat. Rev. Genet. 11, 191-203.
  50. Larsson, A., Peng, S., Persson, H., Rosenbloom, J., Abrams, W.R., Wassberg, E., Thelin, S., Sletten, K., Gerwins, P., and Westermark, P. (2006). Lactadherin binds to elastin--a starting point for medin amyloid formation? Amyloid 13, 78-85.
  51. Laurent, L., Wong, E., Li, G., Huynh, T., Tsirigos, A., Ong, C.T., Low, H.M., Kin Sung, K.W., Rigoutsos, I., Loring, J., et al. (2010). Dynamic changes in the human methylome during differentiation. Genome Res. 20, 320-331.
  52. Li, R., Yu, C., Li, Y., Lam, T.W., Yiu, S.M., Kristiansen, K., and Wang, J. (2009). SOAP2: an improved ultrafast tool for short read alignment. Bioinformatics 25, 1966-1967
  53. Liang, P., Song, F., Ghosh, S., Morien, E., Qin, M., Mahmood, S., Fujiwara, K., Igarashi, J., Nagase, H., and Held, W.A. (2011). Genome-wide survey reveals dynamic widespread tissuespecific changes in DNA methylation during development. BMC Genomics 12, 231.
  54. Lorincz, M.C., Dickerson, D.R., Schmitt, M., and Groudine, M. (2004). Intragenic DNA methylation alters chromatin structure and elongation efficiency in mammalian cells. Nat. Struct. Mol. Biol. 11, 1068-1075.
  55. Louis, E., Raue, U., Yang, Y., Jemiolo, B., and Trappe, S. (2007). Time course of proteolytic, cytokine, and myostatin gene expression after acute exercise in human skeletal muscle. J. Appl. Physiol. 103, 1744-1751.
  56. Matter, K., and Balda, M.S. (2003). Functional analysis of tight junctions. Methods 30, 228-234.
  57. McBride, J.M., Triplett-McBride, T., Davie, A.J., Abernethy, P.J., and Newton, R.U. (2003). Characteristics of titin in strength and power athletes. Eur. J. Appl. Physiol. 88, 553-557
  58. McGivney, B.A., Eivers, S.S., MacHugh, D.E., MacLeod, J.N., O'Gorman, G.M., Park, S.D., Katz, L.M., and Hill, E.W. (2009). Transcriptional adaptations following exercise in thoroughbred horse skeletal muscle highlights molecular mechanisms that lead to muscle hypertrophy. BMC Genomics 10, 638
  59. McGivney, B.A., McGettigan, P.A., Browne, J.A., Evans, A.C., Fonseca, R.G., Loftus, B.J., Lohan, A., MacHugh, D.E., Murphy, B.A., Katz, L.M., et al. (2010). Characterization of the equine skeletal muscle transcriptome identifies novel functional responses to exercise training. BMC Genomics 11, 398
  60. Noble, G.K., Houghton, E., Roberts, C.J., Faustino-Kemp, J., de Kock, S.S., Swanepoel, B.C., and Sillence, M.N. (2007). Effect of exercise, training, circadian rhythm, age, and sex on insulinlike growth factor-1 in the horse. J. Anim. Sci. 85, 163-171.
  61. Nostell, K.E., Essen-Gustavsson, B., and Brojer, J.T. (2012). Repeated post-exercise administration with a mixture of leucine and glucose alters the plasma amino acid profile in Standardbred trotters. Acta Vet. Scand. 54, 7
  62. Olson, T.M., and Terzic, A. (2010). Human K(ATP) channelopathies: diseases of metabolic homeostasis. Pflugers Arch. 460, 295-306.
  63. Padalino, B., Rubino, G., Lacinio, R., and Petazzi, F. (2014). Observations on the hematology of standardbred horses in training and racing in Southern Italy. J. Equine Vet. Sci. 34, 398-402.
  64. Park, K.D., Park, J., Ko, J., Kim, B.C., Kim, H.S., Ahn, K., Do, K.T., Choi, H., Kim, H.M., Song, S., et al. (2012). Whole transcriptome analyses of six thoroughbred horses before and after exercise using RNA-Seq. BMC Genomics 13, 473.
  65. Petersen, J.L., Mickelson, J.R., Rendahl, A.K., Valberg, S.J., Andersson, L.S., Axelsson, J., Bailey, E., Bannasch, D., Binns, M.M., Borges, A.S., et al. (2013). Genome-wide analysis reveals selection for important traits in domestic horse breeds. PLoS Genet. 9, e1003211.
  66. Pomraning, K.R., Smith, K.M. and Freitag, M. (2009). Genomewide high throughput analysis of DNA methylation in eukaryotes. Methods 47, 142-150.
  67. Radom-Aizik, S., Zaldivar, F., Jr., Leu, S.Y., and Cooper, D.M. (2009). A brief bout of exercise alters gene expression and distinct gene pathways in peripheral blood mononuclear cells of early-and late-pubertal females. J. Appl. Physiol. 107, 168-175.
  68. Roberts, M.D., Dalbo, V.J., Hassell, S.E., and Kerksick, C.M. (2009). The expression of androgen-regulated genes before and after a resistance exercise bout in younger and older men. J. Strength Cond. Res. 23, 1060-1067
  69. Russell, A.P., Feilchenfeldt, J., Schreiber, S., Praz, M., Crettenand, A., Gobelet, C., Meier, C.A., Bell, D.R., Kralli, A., Giacobino, J.P., et al. (2003). Endurance training in humans leads to fiber typespecific increases in levels of peroxisome proliferator-activated receptor-gamma coactivator-1 and peroxisome proliferatoractivated receptor-alpha in skeletal muscle. Diabetes 52, 2874-2881.
  70. Russell, A.P., Hesselink, M.K., Lo, S.K., and Schrauwen, P. (2005). Regulation of metabolic transcriptional co-activators and transcription factors with acute exercise. FASEB J. 19, 986-988
  71. Sakamoto, K., Aschenbach, W.G., Hirshman, M.F., and Goodyear, L.J. (2003). Akt signaling in skeletal muscle: regulation by exercise and passive stretch. Am. J. Physiol. Endocrinol. Metab. 285, E1081-1088
  72. Sastry, S.K., and Burridge, K. (2000). Focal adhesions: a nexus for intracellular signaling and cytoskeletal dynamics. Exp. Cell Res. 261, 25-36.
  73. Sati, S., Tanwar, V.S., Kumar, K.A., Patowary, A., Jain, V., Ghosh, S., Ahmad, S., Singh, M., Reddy, S.U., Chandak, G.R., et al. (2012). High resolution methylome map of rat indicates role of intragenic DNA methylation in identification of coding region. PLoS One 7, e31621.
  74. Seip, R.L., Angelopoulos, T.J., and Semenkovich, C.F. (1995). Exercise induces human lipoprotein lipase gene expression in skeletal muscle but not adipose tissue. Am. J. Physiol. 268, E229-236.
  75. Sha, K. (2008). A mechanistic view of genomic imprinting. Annu. Rev. Genomics Hum. Genet. 9, 197-216.
  76. Smith, S.S., Kaplan, B.E., Sowers, L.C., and Newman, E.M. (1992). Mechanism of human methyl-directed DNA methyltransferase and the fidelity of cytosine methylation. Proc. Natl. Acad. Sci. USA 89, 4744-4748
  77. Stegh, A.H., Schickling, O., Ehret, A., Scaffidi, C., Peterhansel, C., Hofmann, T.G., Grummt, I., Krammer, P.H., and Peter, M.E. (1998). DEDD, a novel death effector domain-containing protein, targeted to the nucleolus. EMBO J. 17, 5974-5986.
  78. Sun, J., Nishiyama, T., Shimizu, K., and Kadota, K. (2013). TCC: an R package for comparing tag count data with robust normalization strategies. BMC Bioinformatics 14, 219
  79. Suontama, M., van der Werf, J.H., Juga, J., and Ojala, M. (2013). Genetic correlations for foal and studbook traits with racing traits and implications for selection strategies in the Finnhorse and Standardbred trotter. J. Anim. Breed Genet. 130, 178-189
  80. Tucker, K.L. (2001). Methylated cytosine and the brain: a new base for neuroscience. Neuron 30, 649-652.
  81. Vider, J., Lehtmaa, J., Kullisaar, T., Vihalemm, T., Zilmer, K., Kairane, C., Landor, A., Karu, T., and Zilmer, M. (2001). Acute immune response in respect to exercise-induced oxidative stress. Pathophysiology 7, 263-270.
  82. Walsh, C.P., Chaillet, J.R., and Bestor, T.H. (1998). Transcription of IAP endogenous retroviruses is constrained by cytosine methylation. Nat. Genet. 20, 116-117
  83. Yan, H., Kikuchi, S., Neumann, P., Zhang, W., Wu, Y., Chen, F., and Jiang, J. (2010). Genome-wide mapping of cytosine methylation revealed dynamic DNA methylation patterns associated with genes and centromeres in rice. Plant J. 63, 353-365.
  84. Zeilinger, S., Kuhnel, B., Klopp, N., Baurecht, H., Kleinschmidt, A., Gieger, C., Weidinger, S., Lattka, E., Adamski, J., Peters, A., et al. (2013). Tobacco smoking leads to extensive genome-wide changes in DNA methylation. PLoS One 8, e63812.
  85. Zhang, Y., Liu, T., Meyer, C.A., Eeckhoute, J., Johnson, D.S., Bernstein, B.E., Nusbaum, C., Myers, R.M., Brown, M., Li, W., et al. (2008). Model-based analysis of ChIP-Seq (MACS). Genome Biol. 9, R137
  86. Zhang, F.F., Cardarelli, R., Carroll, J., Fulda, K.G., Kaur, M., Gonzalez, K., Vishwanatha, J.K., Santella, R.M., and Morabia, A. (2011). Significant differences in global genomic DNA methylation by gender and race/ethnicity in peripheral blood. Epigenetics 6, 623-629
  87. Norton, L.E., and Layman, D.K. (2006). Leucine regulates translation initiation of protein synthesis in skeletal muscle after exercise. J. Nutr. 136, 533S-537S.

Cited by

  1. Fipronil-induced enantioselective developmental toxicity to zebrafish embryo-larvae involves changes in DNA methylation vol.7, pp.1, 2017,
  2. Nuclear and Mitochondrial DNA Methylation Patterns Induced by Valproic Acid in Human Hepatocytes 2017,
  3. Identification and Expression of Equine MER-Derived miRNAs vol.40, pp.4, 2017,
  4. Global analysis of DNA methylation in young (J1) and senescent (J2) Gossypium hirsutum L. cotyledons by MeDIP-Seq vol.12, pp.7, 2017,
  5. Epigenetic regulatory elements: Recent advances in understanding their mode of action and use for recombinant protein production in mammalian cells vol.10, pp.7, 2015,
  6. Comparative analysis on genome-wide DNA methylation in longissimus dorsi muscle between Small Tailed Han and Dorper×Small Tailed Han crossbred sheep vol.30, pp.11, 2017,