Genome-wide analysis of DNA methylation before- and after exercise in the thoroughbred horse with MeDIP-seq

Molecules and Cells

Volumn 38, Issue 3, 2015, Pages 210-220

  Gim, Jeong An ^a   Hong, Chang Pyo ^b   Kim, Dae Soo ^c   Moon, Jae Woo ^b   Choi, Yuri ^a   Eo, Jungwoo ^a   Kwon, Yun Jeong ^a   Lee, Ja Rang ^a   Jung, Yi Deun ^a   Bae, Jin Han ^a   Choi, Bong Hwan ^d   Ko, Junsu ^b   Song, Sanghoon ^b   Ahn, Kung ^b   Ha, Hong Seok ^e   Yang, Young Mok ^f   Lee, Hak Kyo ^g   Park, Kyung Do ^g   Do, Kyoung Tag ^h   Han, Kyudong ⁱ   Yi, Joo Mi ^j   Cha, Hee Jae ^k   Ayarpadikannan, Selvam ^a   Cho, Byung Wook ^a   Bhak, Jong ^b,l   Kim, Heui Soo ^a   more..

^a Pusan National University   (South Korea)

^b TBI   (South Korea)

^c Korea Research Institute of Bioscience and Biotechnology (KRIBB)   (South Korea)

^d National Institute of Animal Science   (South Korea)

^e Life Sciences Building Rutgers University   (United States)

^f Konkuk University School of Medicine   (South Korea)

^g Hankyong National University   (South Korea)

^h Sorabol College   (South Korea)

ⁱ Dankook University   (South Korea)

^j Dongnam Institute of Radiological and Medical Science   (South Korea)

^k Kosin University College of Medicine   (South Korea)

^l Ulsan National Institute of Science and Technology   (South Korea)

more..

Author keywords

DNA methylation; Exercise; MeDIP Seq; Thoroughbred horse; Transposable elements

Indexed keywords

ADHESION; BLOOD; CELL DIVISION; CPG ISLAND; DNA METHYLATION; DNA STRUCTURE; EPIGENETICS; EXERCISE; GENE ONTOLOGY; GENOME; IMMUNOPRECIPITATION; THOROUGHBRED HORSE; TRANSPOSON; ANIMAL; DNA SEQUENCE; FEMALE; GENETICS; HORSE; MALE; MOTOR ACTIVITY; NUCLEOTIDE SEQUENCE; SEXUAL DEVELOPMENT;

DNA;

ANIMALS; BASE SEQUENCE; DNA; DNA METHYLATION; EPIGENOMICS; FEMALE; GENE ONTOLOGY; HORSES; MALE; MOTOR ACTIVITY; PHYSICAL EXERTION; SEQUENCE ANALYSIS, DNA; SEX CHARACTERISTICS;

EID: 84935691832     PISSN: 10168478     EISSN: 02191032     Source Type: Journal    
DOI: 10.14348/molcells.2015.2138     Document Type: Article

References (87)

1. 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.
2. Allen, D.G, Lamb, GD., and Westerblad, H. (2008). Impaired calcium release during fatigue. J. Appl. Physiol. 104, 296-305.
3. 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 genome- scale strategies reveal gene-body methylation signatures in human cells. Nat. Biotechnol. 27, 361-368.
4. 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.
5. Bird, A. (2002). DNA methylation patterns and epigenetic memory. Genes Dev. 16, 6-21.
6. 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.
7. 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.
8. 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.
9. Carlsson, L., Yu, J.G, and Thornell, L.E. (2008). New aspects of obscurin in human striated muscles. Histochem. Cell Biol. 130, 91-103.
10. 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.
11. Chang, S.C., Tucker, T., Thorogood, N.P., and Brown, C.J. (2006). Mechanisms of X-chromosome inactivation. Front. Biosci. 11, 852-866.
12. 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.
13. +, K+-distribution in muscle function. The FEPS lecture-Bratislava 2007. Acta Physiol. 192, 339-349.
14. 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.
15. 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.
16. Dawson, M.A., and Kouzarides, T. (2012). Cancer epigenetics: from mechanism to therapy. Cell 150, 12-27.
17. 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.
18. Dempsey, J.A., and Wagner, P.D. (1999). Exercise-induced arterial hypoxemia. J. Appl. Physiol. 87, 1997-2006.
19. 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.
20. 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.
21. 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.
22. 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.
23. 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.
24. 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.
25. Feber, A., Wilson, GA., 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.
26. Gano, L.B., Donato, A.J., Pierce, GL., 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.
27. Gao, L., Geng, Y, Li, B., Chen, J., and Yang, J. (2010). Genome- wide 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.
28. 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.
29. Gardiner, P., Dai, Y, and Heckman, C.J. (2006). Effects of exercise training on alpha-motoneurons. J. Appl. Physiol. 101, 1228-1236.
30. 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.
31. 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.
32. 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 cholangio- carcinoma target the Wnt signaling pathway. Hepatology 59, 544-554.
33. 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.
34. 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.
35. Griffin, M., Casadio, R., and Bergamini, C.M. (2002). Transglutaminases: nature’s biological glues. Biochem. J. 368, 377-396.
36. 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.
37. Handschin, C., Kobayashi, Y.M., Chin, S., Seale, P., Campbell, K.P., and Spiegelman, B.M. (2007b). PGC-1 alpha regulates the neuromuscular junction program and ameliorates Duchenne muscular dystrophy. Genes Dev. 21, 770-783.
38. 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.
39. 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 perfor-mance. Anim. Genet. 41 Suppl 2, 56-63.
40. Hsiung, D.T., Marsit, C.J., Houseman, E.A., Eddy, K., Furniss, C.S., McClean, M.D., and Kelsey, K.T. (2007). Global DNA methy- lation level in whole blood as a biomarker in head and neck squamous cell carcinoma. Cancer Epidemiol. Biomarkers Prev. 16, 108-114.
41. 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.
42. 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.
43. 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.
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 Wester- mark, 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, 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 tissue- specific 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, GM., 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, 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. 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.
62. 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 Standard- bred trotters. Acta Vet. Scand. 54, 7.
63. Olson, T.M., and Terzic, A. (2010). Human K(ATP) channelo-pathies: diseases of metabolic homeostasis. Pflugers Arch. 460, 295-306.
64. 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.
65. 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.
66. Petersen, J.L., Mickelson, J.R., Rendahl, A.K., Valberg, S.J., Ander- sson, 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.
67. Pomraning, K.R., Smith, K.M. and Freitag, M. (2009). Genome- wide high throughput analysis of DNA methylation in eukaryotes. Methods 47, 142-150.
68. 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.
69. 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.
70. 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 type- specific increases in levels of peroxisome proliferator-activated receptor-gamma coactivator-1 and peroxisome proliferator- activated receptor-alpha in skeletal muscle. Diabetes 52, 2874-2881.
71. 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.
72. 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.
73. Sastry, S.K., and Burridge, K. (2000). Focal adhesions: a nexus for intracellular signaling and cytoskeletal dynamics. Exp. Cell Res. 261, 25-36.
74. Sati, S., Tanwar, V.S., Kumar, K.A., Patowary, A., Jain, V., Ghosh, S., Ahmad, S., Singh, M., Reddy, S.U., Chandak, GR., et al. (2012). High resolution methylome map of rat indicates role of intragenic DNA methylation in identification of coding region. PLoS One 7, e31621.
75. 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.
76. Sha, K. (2008). A mechanistic view of genomic imprinting. Annu. Rev. Genomics Hum. Genet. 9, 197-216.
77. 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.
78. 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.
79. 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.
80. 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.
81. Tucker, K.L. (2001). Methylated cytosine and the brain: a new base for neuroscience. Neuron 30, 649-652.
82. 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.
83. 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.
84. 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.
85. 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.
86. 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.
87. 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 methy-lation by gender and race/ethnicity in peripheral blood. Epigenetics 6, 623-629.