Advertisement

Asthma Epigenetics

  • Muhammad T. Salam
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 795)

Abstract

Asthma is the most common chronic disease of childhood, and a growing body of evidence indicates that epigenetic variations may mediate the effects of environmental exposures on the development and natural history of asthma. Epigenetics is the study of mitotically or meiotically heritable changes in gene expression that occur without directly altering the DNA sequence. DNA methylation, histone modifications and miroRNAs are major epigenetic variations in humans that are currently being investigated for asthma etiology and natural history. DNA methylation results from addition of a methyl group to the 5 position of a cytosine ring and occurs almost exclusively on a cytosine in a CpG dinucleotide. Histone modifications involve posttranslational modifications such as acetylation, methylation, phosphorylation and ubiquitination on the tails of core histones. MicroRNAs are short ~22 nucleotide long, non-coding, single-stranded RNAs that binds to complementary sequences in the target mRNAs, usually resulting in gene silencing. While many studies have documented relationships of environmental exposures that have been implicated in asthma etiology with epigenetic alterations, to date, few studies have directly linked epigenetic variations with asthma development. There are several methodological challenges in studying the epigenetics of asthma. In this chapter, the influence of epigenetic variations on asthma pathophysiology, methodological concerns in conducting epigenetic research and future direction of asthma epigenetics research are discussed.

Keywords

Epigenetics DNA methylation CpG island Histone acetylation Histone acetyltransferase (HAT) Histone deacetylase (HDAC) Sirtuin1 (SIRT1) microRNA (miRNA) Single nucleotide polymorphism (SNP) Telomerase CpG pyrosequencing Chromatin immunoprecipitation-next generation sequencing (ChIP-Seq) 

Notes

Acknowledgment

Some texts are reproduced from Epigenomics, August 2012, Vol. 4, No. 4, Pages 415–429 with permission of Future Medicine Ltd.

References

  1. Adriaens ME, Jaillard M, Eijssen LM et al (2012) An evaluation of two-channel ChIP-on-chip and DNA methylation microarray normalization strategies. BMC Genomics 13:42PubMedCrossRefGoogle Scholar
  2. Alder JK, Guo N, Kembou F et al (2011) Telomere length is a determinant of emphysema susceptibility. Am J Respir Crit Care Med 184:904–12PubMedCrossRefGoogle Scholar
  3. Allsopp RC, Vaziri H, Patterson C et al (1992) Telomere length predicts replicative capacity of human fibroblasts. Proc Natl Acad Sci USA 89:10114–8PubMedCrossRefGoogle Scholar
  4. Bazzoni F, Rossato M, Fabbri M et al (2009) Induction and regulatory function of miR-9 in human monocytes and neutrophils exposed to proinflammatory signals. Proc Natl Acad Sci USA 106:5282–7PubMedCrossRefGoogle Scholar
  5. Bhandare R, Schug J, Le Lay J et al (2010) Genome-wide analysis of histone modifications in human pancreatic islets. Genome Res 20:428–33PubMedCrossRefGoogle Scholar
  6. Bird A (2007) Perceptions of epigenetics. Nature 447:396–8PubMedCrossRefGoogle Scholar
  7. Butler CA, McQuaid S, Taggart CC et al (2012) Glucocorticoid receptor β and histone deacetylase 1 and 2 expression in the airways of severe asthma. Thorax 67:392–8Google Scholar
  8. Campan M, Weisenberger DJ, Trinh B et al (2009) MethyLight. Methods Mol Biol 507:325–37PubMedCrossRefGoogle Scholar
  9. Chawes BL, Bonnelykke K, Kreiner-Moller E et al (2010) Children with allergic and nonallergic rhinitis have a similar risk of asthma. J Allergy Clin Immunol 126(567–73):e1–8PubMedGoogle Scholar
  10. Chen RF, Huang HC, Ou CY et al (2010) MicroRNA-21 expression in neonatal blood associated with antenatal immunoglobulin E production and development of allergic rhinitis. Clin Exp Allergy 40:1482–90PubMedCrossRefGoogle Scholar
  11. Chiba Y, Tanabe M, Goto K et al (2009) Down-regulation of miR-133a contributes to up-regulation of Rhoa in bronchial smooth muscle cells. Am J Respir Crit Care Med 180:713–9PubMedCrossRefGoogle Scholar
  12. Choi JH, Oh SW, Kang MS et al (2005) Trichostatin A attenuates airway inflammation in mouse asthma model. Clin Exp Allergy 35:89–96PubMedCrossRefGoogle Scholar
  13. Cokus SJ, Feng S, Zhang X et al (2008) Shotgun bisulphite sequencing of the Arabidopsis genome reveals DNA methylation patterning. Nature 452:215–9PubMedCrossRefGoogle Scholar
  14. Collison A, Herbert C, Siegle JS et al (2011a) Altered expression of microRNA in the airway wall in chronic asthma: miR-126 as a potential therapeutic target. BMC Pulm Med 11:29PubMedCrossRefGoogle Scholar
  15. Collison A, Mattes J, Plank M et al (2011b) Inhibition of house dust mite-induced allergic airways disease by antagonism of microRNA-145 is comparable to glucocorticoid treatment. J Allergy Clin Immunol 128(160–67):e4PubMedGoogle Scholar
  16. Cortessis VK, Thomas DC, Levine AJ et al (2012) Environmental epigenetics: prospects for studying epigenetic mediation of exposure-response relationships. Hum Genet 131:1565–89PubMedCrossRefGoogle Scholar
  17. Deng J, Shoemaker R, Xie B et al (2009) Targeted bisulfite sequencing reveals changes in DNA methylation associated with nuclear reprogramming. Nat Biotechnol 27:353–60PubMedCrossRefGoogle Scholar
  18. Duan R, Pak C, Jin P (2007) Single nucleotide polymorphism associated with mature miR-125a alters the processing of pri-miRNA. Hum Mol Genet 16:1124–31PubMedCrossRefGoogle Scholar
  19. Egelhofer TA, Minoda A, Klugman S et al (2011) An assessment of histone-modification antibody quality. Nat Struct Mol Biol 18:91–3PubMedCrossRefGoogle Scholar
  20. Grausenburger R, Bilic I, Boucheron N et al (2010) Conditional deletion of histone deacetylase 1 in T cells leads to enhanced airway inflammation and increased Th2 cytokine production. J Immunol 185:3489–97PubMedCrossRefGoogle Scholar
  21. Gutcher I, Donkor MK, Ma Q et al (2011) Autocrine transforming growth factor-beta1 promotes in vivo Th17 cell differentiation. Immunity 34:396–408PubMedCrossRefGoogle Scholar
  22. Harris RA, Wang T, Coarfa C et al (2010) Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications. Nat Biotechnol 28:1097–105PubMedCrossRefGoogle Scholar
  23. Hollingsworth JW, Maruoka S, Boon K et al (2008) In utero supplementation with methyl donors enhances allergic airway disease in mice. J Clin Invest 118:3462–9PubMedGoogle Scholar
  24. Hou L, Wang S, Dou C et al (2012) Air pollution exposure and telomere length in highly exposed subjects in Beijing, China: a repeated-measure study. Environ Int 48:71–7PubMedCrossRefGoogle Scholar
  25. Houben JM, Mercken EM, Ketelslegers HB et al (2009) Telomere shortening in chronic obstructive pulmonary disease. Respir Med 103:230–6PubMedCrossRefGoogle Scholar
  26. Hoxha M, Dioni L, Bonzini M et al (2009) Association between leukocyte telomere shortening and exposure to traffic pollution: a cross-sectional study on traffic officers and indoor office workers. Environ Health 8:41PubMedCrossRefGoogle Scholar
  27. Irizarry RA, Ladd-Acosta C, Wen B et al (2009) The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores. Nat Genet 41:178–86PubMedCrossRefGoogle Scholar
  28. Ito K, Yamamura S, Essilfie-Quaye S et al (2006) Histone deacetylase 2-mediated deacetylation of the glucocorticoid receptor enables NF-kappaB suppression. J Exp Med 203:7–13PubMedCrossRefGoogle Scholar
  29. Jardim MJ, Dailey L, Silbajoris R et al (2012) Distinct microRNA expression in human airway cells of asthmatic donors identifies a novel asthma-associated gene. Am J Respir Cell Mol Biol 47:536–42PubMedCrossRefGoogle Scholar
  30. Johnson WE, Li C, Rabinovic A (2007) Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics 8:118–27PubMedCrossRefGoogle Scholar
  31. Kim SR, Lee KS, Park SJ et al (2010) Involvement of sirtuin 1 in airway inflammation and hyperresponsiveness of allergic airway disease. J Allergy Clin Immunol 125(449–60):e14PubMedGoogle Scholar
  32. Laird PW (2003) The power and the promise of DNA methylation markers. Nat Rev Cancer 3:253–66PubMedCrossRefGoogle Scholar
  33. Laird PW (2010) Principles and challenges of genomewide DNA methylation analysis. Nat Rev Genet 11:191–203PubMedCrossRefGoogle Scholar
  34. Landt SG, Marinov GK, Kundaje A et al (2012) ChIP-seq guidelines and practices of the ENCODE and modENCODE consortia. Genome Res 22:1813–31PubMedCrossRefGoogle Scholar
  35. Lee KY, Ito K, Hayashi R et al (2006) NF-kappaB and activator protein 1 response elements and the role of histone modifications in IL-1beta-induced TGF-beta1 gene transcription. J Immunol 176:603–15PubMedGoogle Scholar
  36. Levanen B, Bhakta NR, Torregrosa Paredes P et al (2013) Altered microRNA profiles in bronchoalveolar lavage fluid exosomes in asthmatic patients. J Allergy Clin Immunol 131(894–903):e8Google Scholar
  37. Li LB, Leung DY, Martin RJ et al (2010) Inhibition of histone deacetylase 2 expression by elevated glucocorticoid receptor beta in steroid-resistant asthma. Am J Respir Crit Care Med 182:877–83PubMedCrossRefGoogle Scholar
  38. Liu G, Friggeri A, Yang Y et al (2009) miR-147, a microRNA that is induced upon Toll-like receptor stimulation, regulates murine macrophage inflammatory responses. Proc Natl Acad Sci USA 106:15819–24PubMedCrossRefGoogle Scholar
  39. Louafi F, Martinez-Nunez RT, Sanchez-Elsner T (2010) MicroRNA-155 targets SMAD2 and modulates the response of macrophages to transforming growth factor-{beta}. J Biol Chem 285:41328–36PubMedCrossRefGoogle Scholar
  40. Lu TX, Munitz A, Rothenberg ME (2009) MicroRNA-21 is up-regulated in allergic airway inflammation and regulates IL-12p35 expression. J Immunol 182:4994–5002PubMedCrossRefGoogle Scholar
  41. Martinez-Nunez RT, Louafi F, Friedmann PS et al (2009) MicroRNA-155 modulates the pathogen binding ability of dendritic cells (DCs) by down-regulation of DC-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN). J Biol Chem 284:16334–42PubMedCrossRefGoogle Scholar
  42. Mayoral RJ, Deho L, Rusca N et al (2011) MiR-221 influences effector functions and actin cytoskeleton in mast cells. PLoS One 6:e26133PubMedCrossRefGoogle Scholar
  43. McGrath M, Wong JY, Michaud D et al (2007) Telomere length, cigarette smoking, and bladder cancer risk in men and women. Cancer Epidemiol Biomarkers Prev 16:815–9PubMedCrossRefGoogle Scholar
  44. Meissner A, Gnirke A, Bell GW et al (2005) Reduced representation bisulfite sequencing for comparative high-resolution DNA methylation analysis. Nucleic Acids Res 33:5868–77PubMedCrossRefGoogle Scholar
  45. Mikeska T, Felsberg J, Hewitt CA et al (2011) Analysing DNA methylation using bisulphite pyrosequencing. Methods Mol Biol 791:33–53PubMedCrossRefGoogle Scholar
  46. Miller RL, Ho SM (2008) Environmental epigenetics and asthma: current concepts and call for studies. Am J Respir Crit Care Med 177:567–73PubMedCrossRefGoogle Scholar
  47. Mohamed JS, Lopez MA, Boriek AM (2010) Mechanical stretch up-regulates microRNA-26a and induces human airway smooth muscle hypertrophy by suppressing glycogen synthase kinase-3beta. J Biol Chem 285:29336–47PubMedCrossRefGoogle Scholar
  48. Morales E, Bustamante M, Vilahur N et al (2012) DNA hypomethylation at ALOX12 is associated with persistent wheezing in childhood. Am J Respir Crit Care Med 185:937–43PubMedCrossRefGoogle Scholar
  49. Morla M, Busquets X, Pons J et al (2006) Telomere shortening in smokers with and without COPD. Eur Respir J 27:525–8PubMedCrossRefGoogle Scholar
  50. Moschos SA, Williams AE, Perry MM et al (2007) Expression profiling in vivo demonstrates rapid changes in lung microRNA levels following lipopolysaccharide-induced inflammation but not in the anti-inflammatory action of glucocorticoids. BMC Genomics 8:240PubMedCrossRefGoogle Scholar
  51. Nandakumar J, Cech TR (2013) Finding the end: recruitment of telomerase to telomeres. Nat Rev Mol Cell Biol 14:69–82PubMedCrossRefGoogle Scholar
  52. Nicolae D, Cox NJ, Lester LA et al (2005) Fine mapping and positional candidate studies identify HLA-G as an asthma susceptibility gene on chromosome 6p21. Am J Hum Genet 76:349–57PubMedCrossRefGoogle Scholar
  53. Nyren P (2007) The history of pyrosequencing. Methods Mol Biol 373:1–14PubMedCrossRefGoogle Scholar
  54. O’Connell RM, Taganov KD, Boldin MP et al (2007) MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci USA 104:1604–9PubMedCrossRefGoogle Scholar
  55. O’Connell RM, Kahn D, Gibson WS et al (2010) MicroRNA-155 promotes autoimmune inflammation by enhancing inflammatory T cell development. Immunity 33:607–19PubMedCrossRefGoogle Scholar
  56. O’Geen H, Echipare L, Farnham PJ (2011) Using ChIP-seq technology to generate high-resolution profiles of histone modifications. Methods Mol Biol 791:265–86PubMedCrossRefGoogle Scholar
  57. Park PJ (2009) ChIP-seq: advantages and challenges of a maturing technology. Nat Rev Genet 10:669–80PubMedCrossRefGoogle Scholar
  58. Perera F, Herbstman J (2011) Prenatal environmental exposures, epigenetics, and disease. Reprod Toxicol 31:363–73PubMedCrossRefGoogle Scholar
  59. Perera F, Tang WY, Herbstman J et al (2009) Relation of DNA methylation of 5′-CpG island of ACSL3 to transplacental exposure to airborne polycyclic aromatic hydrocarbons and childhood asthma. PLoS One 4:e4488PubMedCrossRefGoogle Scholar
  60. Qin H, Wang L, Feng T et al (2009) TGF-beta promotes Th17 cell development through inhibition of SOCS3. J Immunol 183:97–105PubMedCrossRefGoogle Scholar
  61. Sabbah C, Mazo G, Paccard C et al (2011) SMETHILLIUM: spatial normalization method for Illumina infinium HumanMethylation BeadChip. Bioinformatics 27:1693–5PubMedCrossRefGoogle Scholar
  62. Salam MT, Gauderman WJ, McConnell R et al (2007) Transforming growth factor-β1 C-509T polymorphism, oxidant stress, and early-onset childhood asthma. Am J Respir Crit Care Med 176:1192–9PubMedCrossRefGoogle Scholar
  63. Savale L, Chaouat A, Bastuji-Garin S et al (2009) Shortened telomeres in circulating leukocytes of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 179:566–71PubMedCrossRefGoogle Scholar
  64. Silverman ES, Palmer LJ, Subramaniam V et al (2004) Transforming growth factor-beta1 promoter polymorphism C-509T is associated with asthma. Am J Respir Crit Care Med 169:214–9PubMedCrossRefGoogle Scholar
  65. Solberg OD, Ostrin EJ, Love MI et al (2012) Airway epithelial miRNA expression is altered in asthma. Am J Respir Crit Care Med 186:965–74PubMedCrossRefGoogle Scholar
  66. Su XW, Yang Y, Lv ML et al (2011) Association between single-nucleotide polymorphisms in pre-miRNAs and the risk of asthma in a Chinese population. DNA Cell Biol 30:919–23PubMedCrossRefGoogle Scholar
  67. Sunyer J, Torrent M, Munoz-Ortiz L et al (2005) Prenatal dichlorodiphenyldichloroethylene (DDE) and asthma in children. Environ Health Perspect 113:1787–90PubMedCrossRefGoogle Scholar
  68. Tan Z, Randall G, Fan J et al (2007) Allele-specific targeting of microRNAs to HLA-G and risk of asthma. Am J Hum Genet 81:829–34PubMedCrossRefGoogle Scholar
  69. Tang WY, Levin L, Talaska G et al (2012) Maternal exposure to polycyclic aromatic hydrocarbons and 5′-CpG methylation of interferon-gamma in cord white blood cells. Environ Health Perspect 120(8):1195–2000PubMedCrossRefGoogle Scholar
  70. Taylor KH, Kramer RS, Davis JW et al (2007) Ultradeep bisulfite sequencing analysis of DNA methylation patterns in multiple gene promoters by 454 sequencing. Cancer Res 67:8511–8PubMedCrossRefGoogle Scholar
  71. Tost J, Gut IG (2007) DNA methylation analysis by pyrosequencing. Nat Protoc 2:2265–75PubMedCrossRefGoogle Scholar
  72. Valdes AM, Andrew T, Gardner JP et al (2005) Obesity, cigarette smoking, and telomere length in women. Lancet 366:662–4PubMedCrossRefGoogle Scholar
  73. von Zglinicki T (2002) Oxidative stress shortens telomeres. Trends Biochem Sci 27:339–44CrossRefGoogle Scholar
  74. Wang J, Lunyak VV, Jordan IK (2013) BroadPeak: a novel algorithm for identifying broad peaks in diffuse ChIP-seq datasets. Bioinformatics 29:492–3PubMedCrossRefGoogle Scholar
  75. Waterland RA, Travisano M, Tahiliani KG et al (2008) Methyl donor supplementation prevents transgenerational amplification of obesity. Int J Obes (Lond) 32:1373–9CrossRefGoogle Scholar
  76. Wei G, Hu G, Cui K et al (2012) Genome-wide mapping of nucleosome occupancy, histone modifications, and gene expression using next-generation sequencing technology. Methods Enzymol 513:297–313PubMedCrossRefGoogle Scholar
  77. Williams AE, Larner-Svensson H, Perry MM et al (2009) MicroRNA expression profiling in mild asthmatic human airways and effect of corticosteroid therapy. PLoS One 4:e5889PubMedCrossRefGoogle Scholar
  78. Xie T, Liang J, Liu N et al (2012) MicroRNA-127 Inhibits Lung Inflammation by Targeting IgG Fcgamma Receptor I. J Immunol 188:2437–44PubMedCrossRefGoogle Scholar
  79. Yang SR, Wright J, Bauter M et al (2007) Sirtuin regulates cigarette smoke-induced proinflammatory mediator release via RelA/p65 NF-kappaB in macrophages in vitro and in rat lungs in vivo: implications for chronic inflammation and aging. Am J Physiol Lung Cell Mol Physiol 292:L567–76PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of Preventive Medicine, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA

Personalised recommendations