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Genomic Approach to Asthma pp 69–101Cite as

Epigenetics and Epigenomic Studies in Asthma

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Part of the book series: Translational Bioinformatics ((TRBIO,volume 12))

Abstract

Over 235 million people worldwide suffer from asthma and it is the most common chronic disease among children. As a reversible airway disease, asthma is very heterogeneous due to the complex interactions between host genotype and environmental exposures. The epigenome provides an intriguing pathway through which environmental exposures modifies gene function and contribute to disease risk. In this chapter, I reviewed recent studies demonstrating that epigenetic variation plays an important role in asthma development and severity, possibly through interactions with genetic variations and gene expression. The utilization of epigenetic variation in combination with clinical phenotypes and other molecular markers in separating asthma patient subgroups has been suggested.

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Abbreviations

5mC:

5-methylcytosine

TET:

Ten-eleven Translocation

5hmC:

5’-hydroxymethyl-cytosine

5fC:

5’-formyl-cytosine

5caC:

5’-carboxyl-cytosine

H3K9me:

H3 lysine 9 methylation

H3K4me:

H3 lysine 4 methylation

H3K27me:

H3 lysine 27 methylation

H3K27ac:

H3 lysine 27 acetylation

H3K36me3:

H3 lysine 36 methylation

HKMT:

histone lysine methyltransferase

lncRNAs:

long non-coding RNAs

HELP:

HpaII/MspI digestion with arrays

MRE-seq:

methylation-sensitive restriction enzyme sequencing

MIRA-seq:

methylated CpG island recovery assay-seq

MeDIP-seq:

Methylated DNA immunoprecipitation

Methyl-Cap and MBD-seq:

Methyl-CpG binding domain-based capture and sequencing

SNP:

Single nucleotide polymorphism

LINE1:

Long interspersed nuclear elements

LUMA:

Lumimetric-based Assay

RRBS:

Reduced representation bisulfite sequencing

HPLC:

High-performance liquid chromatography

LC-MS/MS:

Liquid chromatography-mass spectrometry/mass spectrometry

ELISA:

enzyme-linked immunosorbent assay

MALDI-TOF MS:

matrix-assisted laser desorption/ionization- time of flight mass spectrometry

AECs:

airway epithelial cells

PBMCs:

peripheral blood mononuclear cells

meQTL:

methylation quantitative train locus

eQTL:

expression quantitative trait locus

ChIP:

Chromatin immunoprecipitation

X-ChIP:

crosslink ChIP

N-ChIP:

Native ChIP

ULI-NChIP:

ultra-low-input micrococcal nuclease-based native ChIP

RNA-seq:

RNA sequencing

RT-qPCR:

reverse transcription-quantitative PCR

FDR:

false discovery rate

FEV1:

forced expiratory volume in one second

References

  1. Liyanage VR, Jarmasz JS, Murugeshan N, Del Bigio MR, Rastegar M, Davie JR. DNA modifications: function and applications in normal and disease States. Biology. 2014;3(4):670–723. https://doi.org/10.3390/biology3040670.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  2. Klose RJ, Bird AP. Genomic DNA methylation: the mark and its mediators. Trends Biochem Sci. 2006;31(2):89–97. https://doi.org/10.1016/j.tibs.2005.12.008.

    Article  PubMed  CAS  Google Scholar 

  3. Kohli RM, Zhang Y. TET enzymes, TDG and the dynamics of DNA demethylation. Nature. 2013;502(7472):472–9. https://doi.org/10.1038/nature12750.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  4. Huang Y, Rao A. Connections between TET proteins and aberrant DNA modification in cancer. Trends Genet: TIG. 2014;30(10):464–74. https://doi.org/10.1016/j.tig.2014.07.005.

    Article  PubMed  CAS  Google Scholar 

  5. Ko M, An J, Rao A. DNA methylation and hydroxymethylation in hematologic differentiation and transformation. Curr Opin Cell Biol. 2015;37:91–101. https://doi.org/10.1016/j.ceb.2015.10.009.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  6. Patil V, Ward RL, Hesson LB. The evidence for functional non-CpG methylation in mammalian cells. Epigenetics Off J DNA Methylation Soc. 2014;9(6):823–8. https://doi.org/10.4161/epi.28741.

    Article  Google Scholar 

  7. Heyn H, Esteller M. An adenine code for DNA: a second life for N6-methyladenine. Cell. 2015;161(4):710–3. https://doi.org/10.1016/j.cell.2015.04.021.

    Article  PubMed  CAS  Google Scholar 

  8. Yue Y, Liu J, He C. RNA N6-methyladenosine methylation in post-transcriptional gene expression regulation. Genes Dev. 2015;29(13):1343–55. https://doi.org/10.1101/gad.262766.115.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  9. Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti-Filippini J, Nery JR, Lee L, Ye Z, Ngo QM, Edsall L, Antosiewicz-Bourget J, Stewart R, Ruotti V, Millar AH, Thomson JA, Ren B, Ecker JR. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature. 2009;462(7271):315–22. https://doi.org/10.1038/nature08514.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  10. Hu S, Wan J, Su Y, Song Q, Zeng Y, Nguyen HN, Shin J, Cox E, Rho HS, Woodard C, Xia S, Liu S, Lyu H, Ming GL, Wade H, Song H, Qian J, Zhu H. DNA methylation presents distinct binding sites for human transcription factors. elife. 2013;2:e00726. https://doi.org/10.7554/eLife.00726.

    Article  PubMed Central  PubMed  Google Scholar 

  11. Iurlaro M, Ficz G, Oxley D, Raiber EA, Bachman M, Booth MJ, Andrews S, Balasubramanian S, Reik W. A screen for hydroxymethylcytosine and formylcytosine binding proteins suggests functions in transcription and chromatin regulation. Genome Biol. 2013;14(10):R119. https://doi.org/10.1186/gb-2013-14-10-r119.

    Article  PubMed Central  PubMed  Google Scholar 

  12. Spruijt CG, Gnerlich F, Smits AH, Pfaffeneder T, Jansen PW, Bauer C, Munzel M, Wagner M, Muller M, Khan F, Eberl HC, Mensinga A, Brinkman AB, Lephikov K, Muller U, Walter J, Boelens R, van Ingen H, Leonhardt H, Carell T, Vermeulen M. Dynamic readers for 5-(hydroxy)methylcytosine and its oxidized derivatives. Cell. 2013;152(5):1146–59. https://doi.org/10.1016/j.cell.2013.02.004.

    Article  PubMed  CAS  Google Scholar 

  13. Ernst J, Kheradpour P, Mikkelsen TS, Shoresh N, Ward LD, Epstein CB, Zhang X, Wang L, Issner R, Coyne M, Ku M, Durham T, Kellis M, Bernstein BE. Mapping and analysis of chromatin state dynamics in nine human cell types. Nature. 2011;473(7345):43–9. https://doi.org/10.1038/nature09906.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  14. Song Y, Wu F, Wu J. Targeting histone methylation for cancer therapy: enzymes, inhibitors, biological activity and perspectives. J Hematol Oncol. 2016;9(1):49. https://doi.org/10.1186/s13045-016-0279-9.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  15. Bernstein BE, Mikkelsen TS, Xie X, Kamal M, Huebert DJ, Cuff J, Fry B, Meissner A, Wernig M, Plath K, Jaenisch R, Wagschal A, Feil R, Schreiber SL, Lander ES. A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell. 2006;125(2):315–26. https://doi.org/10.1016/j.cell.2006.02.041.

    Article  PubMed  CAS  Google Scholar 

  16. Yuan W, Xu M, Huang C, Liu N, Chen S, Zhu B. H3K36 methylation antagonizes PRC2-mediated H3K27 methylation. J Biol Chem. 2011;286(10):7983–9. https://doi.org/10.1074/jbc.M110.194027.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  17. Seuter S, Heikkinen S, Carlberg C. Chromatin acetylation at transcription start sites and vitamin D receptor binding regions relates to effects of 1alpha, 25-dihydroxyvitamin D3 and histone deacetylase inhibitors on gene expression. Nucleic Acids Res. 2013;41(1):110–24. https://doi.org/10.1093/nar/gks959.

    Article  PubMed  CAS  Google Scholar 

  18. Delcuve GP, Khan DH, Davie JR. Roles of histone deacetylases in epigenetic regulation: emerging paradigms from studies with inhibitors. Clin Epigenetics. 2012;4(1):5. https://doi.org/10.1186/1868-7083-4-5.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  19. Yuan H, Marmorstein R. Histone acetyltransferases: rising ancient counterparts to protein kinases. Biopolymers. 2013;99(2):98–111. https://doi.org/10.1002/bip.22128.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  20. Wapenaar H, Dekker FJ. Histone acetyltransferases: challenges in targeting bi-substrate enzymes. Clin Epigenetics. 2016;8:59. https://doi.org/10.1186/s13148-016-0225-2.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  21. Marmorstein R, Zhou MM. Writers and readers of histone acetylation: structure, mechanism, and inhibition. Cold Spring Harb Perspect Biol. 2014;6(7):a018762. https://doi.org/10.1101/cshperspect.a018762.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  22. Friedmann DR, Marmorstein R. Structure and mechanism of non-histone protein acetyltransferase enzymes. FEBS J. 2013;280(22):5570–81. https://doi.org/10.1111/febs.12373.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  23. Ceccacci E, Minucci S. Inhibition of histone deacetylases in cancer therapy: lessons from leukaemia. Br J Cancer. 2016;114(6):605–11. https://doi.org/10.1038/bjc.2016.36.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  24. Yi X, Jiang XJ, Li XY, Jiang DS. Histone methyltransferases: novel targets for tumor and developmental defects. Am J Transl Res. 2015;7(11):2159–75.

    PubMed Central  PubMed  CAS  Google Scholar 

  25. Farooq Z, Banday S, Pandita TK, Altaf M. The many faces of histone H3K79 methylation. Mutat Res Rev Mutat Res. 2016;768:46–52. https://doi.org/10.1016/j.mrrev.2016.03.005.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  26. He S, Tong Q, Bishop DK, Zhang Y. Histone methyltransferase and histone methylation in inflammatory T-cell responses. Immunotherapy. 2013;5(9):989–1004. https://doi.org/10.2217/imt.13.101.

    Article  PubMed  CAS  Google Scholar 

  27. Atianand MK, Fitzgerald KA. Long non-coding RNAs and control of gene expression in the immune system. Trends Mol Med. 2014;20(11):623–31. https://doi.org/10.1016/j.molmed.2014.09.002.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  28. Willingham AT, Orth AP, Batalov S, Peters EC, Wen BG, Aza-Blanc P, Hogenesch JB, Schultz PG. A strategy for probing the function of noncoding RNAs finds a repressor of NFAT. Science. 2005;309(5740):1570–3. https://doi.org/10.1126/science.1115901.

    Article  PubMed  CAS  Google Scholar 

  29. Xin J, Li J, Feng Y, Wang L, Zhang Y, Yang R. Downregulation of long noncoding RNA HOTAIRM1 promotes monocyte/dendritic cell differentiation through competitively binding to endogenous miR-3960. Onco Targets Ther. 2017;10:1307–15. https://doi.org/10.2147/OTT.S124201.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  30. Wang P, Xue Y, Han Y, Lin L, Wu C, Xu S, Jiang Z, Xu J, Liu Q, Cao X. The STAT3-binding long noncoding RNA lnc-DC controls human dendritic cell differentiation. Science. 2014;344(6181):310–3. https://doi.org/10.1126/science.1251456.

    Article  PubMed  CAS  Google Scholar 

  31. Guttman M, Rinn JL. Modular regulatory principles of large non-coding RNAs. Nature. 2012;482(7385):339–46. https://doi.org/10.1038/nature10887.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  32. Hung T, Chang HY. Long noncoding RNA in genome regulation: prospects and mechanisms. RNA Biol. 2010;7(5):582–5.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  33. Baltimore D, Boldin MP, O’Connell RM, Rao DS, Taganov KD. MicroRNAs: new regulators of immune cell development and function. Nat Immunol. 2008;9(8):839–45. https://doi.org/10.1038/ni.f.209.

    Article  PubMed  CAS  Google Scholar 

  34. Boldin MP, Baltimore D. MicroRNAs, new effectors and regulators of NF-kappaB. Immunol Rev. 2012;246(1):205–20. https://doi.org/10.1111/j.1600-065X.2011.01089.x.

    Article  PubMed  CAS  Google Scholar 

  35. He X, Jing Z, Cheng G. MicroRNAs: new regulators of Toll-like receptor signalling pathways. Biomed Res Int. 2014;2014:945169. https://doi.org/10.1155/2014/945169.

    Article  PubMed Central  PubMed  Google Scholar 

  36. Lu Z, Liu R, Huang E, Chu Y. MicroRNAs: new regulators of IL-22. Cell Immunol. 2016;304-305:1–8. https://doi.org/10.1016/j.cellimm.2016.05.003.

    Article  PubMed  CAS  Google Scholar 

  37. Zhong F, Zhou N, Wu K, Guo Y, Tan W, Zhang H, Zhang X, Geng G, Pan T, Luo H, Zhang Y, Xu Z, Liu J, Liu B, Gao W, Liu C, Ren L, Li J, Zhou J, Zhang H. A SnoRNA-derived piRNA interacts with human interleukin-4 pre-mRNA and induces its decay in nuclear exosomes. Nucleic Acids Res. 2015;43(21):10474–91. https://doi.org/10.1093/nar/gkv954.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  38. Irizarry RA, Ladd-Acosta C, Wen B, Wu Z, Montano C, Onyango P, Cui H, Gabo K, Rongione M, Webster M, Ji H, Potash JB, Sabunciyan S, Feinberg AP. The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores. Nat Genet. 2009;41(2):178–86. https://doi.org/10.1038/ng.298.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  39. Gutierrez-Arcelus M, Ongen H, Lappalainen T, Montgomery SB, Buil A, Yurovsky A, Bryois J, Padioleau I, Romano L, Planchon A, Falconnet E, Bielser D, Gagnebin M, Giger T, Borel C, Letourneau A, Makrythanasis P, Guipponi M, Gehrig C, Antonarakis SE, Dermitzakis ET. Tissue-specific effects of genetic and epigenetic variation on gene regulation and splicing. PLoS Genet. 2015;11(1):e1004958. https://doi.org/10.1371/journal.pgen.1004958.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  40. Li WV, Razaee ZS, Li JJ. Epigenome overlap measure (EPOM) for comparing tissue/cell types based on chromatin states. BMC Genomics. 2016;17(Suppl 1):10. https://doi.org/10.1186/s12864-015-2303-9.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  41. Chen Y, Breeze CE, Zhen S, Beck S, Teschendorff AE. Tissue-independent and tissue-specific patterns of DNA methylation alteration in cancer. Epigenetics Chromatin. 2016;9:10. https://doi.org/10.1186/s13072-016-0058-4.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  42. Bjornsson HT, Fallin MD, Feinberg AP. An integrated epigenetic and genetic approach to common human disease. Trends Genet TIG. 2004;20(8):350–8. https://doi.org/10.1016/j.tig.2004.06.009.

    Article  PubMed  CAS  Google Scholar 

  43. Cheung WA, Shao X, Morin A, Siroux V, Kwan T, Ge B, Aissi D, Chen L, Vasquez L, Allum F, Guenard F, Bouzigon E, Simon MM, Boulier E, Redensek A, Watt S, Datta A, Clarke L, Flicek P, Mead D, Paul DS, Beck S, Bourque G, Lathrop M, Tchernof A, Vohl MC, Demenais F, Pin I, Downes K, Stunnenberg HG, Soranzo N, Pastinen T, Grundberg E. Functional variation in allelic methylomes underscores a strong genetic contribution and reveals novel epigenetic alterations in the human epigenome. Genome Biol. 2017;18(1):50. https://doi.org/10.1186/s13059-017-1173-7.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  44. Feinberg AP, Fallin MD. Epigenetics at the crossroads of genes and the environment. JAMA. 2015;314(11):1129–30. https://doi.org/10.1001/jama.2015.10414.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  45. Huether R, Dong L, Chen X, Wu G, Parker M, Wei L, Ma J, Edmonson MN, Hedlund EK, Rusch MC, Shurtleff SA, Mulder HL, Boggs K, Vadordaria B, Cheng J, Yergeau D, Song G, Becksfort J, Lemmon G, Weber C, Cai Z, Dang J, Walsh M, Gedman AL, Faber Z, Easton J, Gruber T, Kriwacki RW, Partridge JF, Ding L, Wilson RK, Mardis ER, Mullighan CG, Gilbertson RJ, Baker SJ, Zambetti G, Ellison DW, Zhang J, Downing JR. The landscape of somatic mutations in epigenetic regulators across 1,000 paediatric cancer genomes. Nat Commun. 2014;5:3630. https://doi.org/10.1038/ncomms4630.

    Article  PubMed  CAS  Google Scholar 

  46. Busche S, Ge B, Vidal R, Spinella JF, Saillour V, Richer C, Healy J, Chen SH, Droit A, Sinnett D, Pastinen T. Integration of high-resolution methylome and transcriptome analyses to dissect epigenomic changes in childhood acute lymphoblastic leukemia. Cancer Res. 2013;73(14):4323–36. https://doi.org/10.1158/0008-5472.CAN-12-4367.

    Article  PubMed  CAS  Google Scholar 

  47. Zuckerman T, Rowe JM. Pathogenesis and prognostication in acute lymphoblastic leukemia. F1000prime Rep. 2014;6:59. https://doi.org/10.12703/P6-59.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  48. Laird PW. Principles and challenges of genomewide DNA methylation analysis. Nat Rev Genet. 2010;11(3):191–203. https://doi.org/10.1038/nrg2732.

    Article  PubMed  CAS  Google Scholar 

  49. Khulan B, Thompson RF, Ye K, Fazzari MJ, Suzuki M, Stasiek E, Figueroa ME, Glass JL, Chen Q, Montagna C, Hatchwell E, Selzer RR, Richmond TA, Green RD, Melnick A, Greally JM. Comparative isoschizomer profiling of cytosine methylation: the HELP assay. Genome Res. 2006;16(8):1046–55. https://doi.org/10.1101/gr.5273806.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  50. Brunner AL, Johnson DS, Kim SW, Valouev A, Reddy TE, Neff NF, Anton E, Medina C, Nguyen L, Chiao E, Oyolu CB, Schroth GP, Absher DM, Baker JC, Myers RM. Distinct DNA methylation patterns characterize differentiated human embryonic stem cells and developing human fetal liver. Genome Res. 2009;19(6):1044–56. https://doi.org/10.1101/gr.088773.108.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  51. Maunakea AK, Nagarajan RP, Bilenky M, Ballinger TJ, D’Souza C, Fouse SD, Johnson BE, Hong C, Nielsen C, Zhao Y, Turecki G, Delaney A, Varhol R, Thiessen N, Shchors K, Heine VM, Rowitch DH, Xing X, Fiore C, Schillebeeckx M, Jones SJ, Haussler D, Marra MA, Hirst M, Wang T, Costello JF. Conserved role of intragenic DNA methylation in regulating alternative promoters. Nature. 2010;466(7303):253–7. https://doi.org/10.1038/nature09165.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  52. Irizarry RA, Ladd-Acosta C, Carvalho B, Wu H, Brandenburg SA, Jeddeloh JA, Wen B, Feinberg AP. Comprehensive high-throughput arrays for relative methylation (CHARM). Genome Res. 2008;18(5):780–90. https://doi.org/10.1101/gr.7301508.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  53. Ladd-Acosta C, Aryee MJ, Ordway JM, Feinberg AP. Comprehensive high-throughput arrays for relative methylation (CHARM). Curr Protoc Hum Genet Chapter 20:Unit 20 21 21-19. 2010. doi:https://doi.org/10.1002/0471142905.hg2001s65

  54. Mukhopadhyay R, Yu W, Whitehead J, Xu J, Lezcano M, Pack S, Kanduri C, Kanduri M, Ginjala V, Vostrov A, Quitschke W, Chernukhin I, Klenova E, Lobanenkov V, Ohlsson R. The binding sites for the chromatin insulator protein CTCF map to DNA methylation-free domains genome-wide. Genome Res. 2004;14(8):1594–602. https://doi.org/10.1101/gr.2408304.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  55. Weber M, Davies JJ, Wittig D, Oakeley EJ, Haase M, Lam WL, Schubeler D. Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells. Nat Genet. 2005;37(8):853–62. https://doi.org/10.1038/ng1598.

    Article  PubMed  CAS  Google Scholar 

  56. Cross SH, Charlton JA, Nan X, Bird AP. Purification of CpG islands using a methylated DNA binding column. Nat Genet. 1994;6(3):236–44. https://doi.org/10.1038/ng0394-236.

    Article  PubMed  CAS  Google Scholar 

  57. Jorgensen HF, Adie K, Chaubert P, Bird AP. Engineering a high-affinity methyl-CpG-binding protein. Nucleic Acids Res. 2006;34(13):e96. https://doi.org/10.1093/nar/gkl527.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  58. Gebhard C, Schwarzfischer L, Pham TH, Schilling E, Klug M, Andreesen R, Rehli M. Genome-wide profiling of CpG methylation identifies novel targets of aberrant hypermethylation in myeloid leukemia. Cancer Res. 2006;66(12):6118–28. https://doi.org/10.1158/0008-5472.CAN-06-0376.

    Article  PubMed  CAS  Google Scholar 

  59. Rauch TA, Pfeifer GP. The MIRA method for DNA methylation analysis. Methods Mol Biol. 2009;507:65–75. https://doi.org/10.1007/978-1-59745-522-0_6.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  60. Taylor KH, Kramer RS, Davis JW, Guo J, Duff DJ, Xu D, Caldwell CW, Shi H. Ultradeep bisulfite sequencing analysis of DNA methylation patterns in multiple gene promoters by 454 sequencing. Cancer Res. 2007;67(18):8511–8. https://doi.org/10.1158/0008-5472.CAN-07-1016.

    Article  PubMed  CAS  Google Scholar 

  61. Li D, Zhang B, Xing X, Wang T. Combining MeDIP-seq and MRE-seq to investigate genome-wide CpG methylation. Methods. 2015;72:29–40. https://doi.org/10.1016/j.ymeth.2014.10.032.

    Article  PubMed  CAS  Google Scholar 

  62. Plongthongkum N, Diep DH, Zhang K. Advances in the profiling of DNA modifications: cytosine methylation and beyond. Nat Rev Genet. 2014;15(10):647–61. https://doi.org/10.1038/nrg3772.

    Article  PubMed  CAS  Google Scholar 

  63. Yu M, Hon GC, Szulwach KE, Song CX, Zhang L, Kim A, Li X, Dai Q, Shen Y, Park B, Min JH, Jin P, Ren B, He C. Base-resolution analysis of 5-hydroxymethylcytosine in the mammalian genome. Cell. 2012;149(6):1368–80. https://doi.org/10.1016/j.cell.2012.04.027.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  64. Booth MJ, Marsico G, Bachman M, Beraldi D, Balasubramanian S. Quantitative sequencing of 5-formylcytosine in DNA at single-base resolution. Nat Chem. 2014;6(5):435–40. https://doi.org/10.1038/nchem.1893.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  65. Booth MJ, Ost TW, Beraldi D, Bell NM, Branco MR, Reik W, Balasubramanian S. Oxidative bisulfite sequencing of 5-methylcytosine and 5-hydroxymethylcytosine. Nat Protoc. 2013;8(10):1841–51. https://doi.org/10.1038/nprot.2013.115.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  66. Clark SJ, Smallwood SA, Lee HJ, Krueger F, Reik W, Kelsey G. Genome-wide base-resolution mapping of DNA methylation in single cells using single-cell bisulfite sequencing (scBS-seq). Nat Protoc. 2017;12(3):534–47. https://doi.org/10.1038/nprot.2016.187.

    Article  PubMed  CAS  Google Scholar 

  67. Angermueller C, Clark SJ, Lee HJ, Macaulay IC, Teng MJ, Hu TX, Krueger F, Smallwood S, Ponting CP, Voet T, Kelsey G, Stegle O, Reik W. Parallel single-cell sequencing links transcriptional and epigenetic heterogeneity. Nat Methods. 2016;13(3):229–32. https://doi.org/10.1038/nmeth.3728.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  68. Meissner A, Gnirke A, Bell GW, Ramsahoye B, Lander ES, Jaenisch R. Reduced representation bisulfite sequencing for comparative high-resolution DNA methylation analysis. Nucleic Acids Res. 2005;33(18):5868–77. https://doi.org/10.1093/nar/gki901.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  69. Gu H, Smith ZD, Bock C, Boyle P, Gnirke A, Meissner A. Preparation of reduced representation bisulfite sequencing libraries for genome-scale DNA methylation profiling. Nat Protoc. 2011;6(4):468–81. https://doi.org/10.1038/nprot.2010.190.

    Article  PubMed  CAS  Google Scholar 

  70. Wang J, Xia Y, Li L, Gong D, Yao Y, Luo H, Lu H, Yi N, Wu H, Zhang X, Tao Q, Gao F. Double restriction-enzyme digestion improves the coverage and accuracy of genome-wide CpG methylation profiling by reduced representation bisulfite sequencing. BMC Genomics. 2013;14:11. https://doi.org/10.1186/1471-2164-14-11.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  71. Karimi M, Johansson S, Stach D, Corcoran M, Grander D, Schalling M, Bakalkin G, Lyko F, Larsson C, Ekstrom TJ. LUMA (LUminometric Methylation Assay)--a high throughput method to the analysis of genomic DNA methylation. Exp Cell Res. 2006;312(11):1989–95. https://doi.org/10.1016/j.yexcr.2006.03.006.

    Article  PubMed  CAS  Google Scholar 

  72. Suchiman HE, Slieker RC, Kremer D, Slagboom PE, Heijmans BT, Tobi EW. Design, measurement and processing of region-specific DNA methylation assays: the mass spectrometry-based method EpiTYPER. Front Genet. 2015;6:287. https://doi.org/10.3389/fgene.2015.00287.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  73. Jones PA. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet. 2012;13(7):484–92. https://doi.org/10.1038/nrg3230.

    Article  PubMed  CAS  Google Scholar 

  74. van Eijk KR, de Jong S, Boks MP, Langeveld T, Colas F, Veldink JH, de Kovel CG, Janson E, Strengman E, Langfelder P, Kahn RS, van den Berg LH, Horvath S, Ophoff RA. Genetic analysis of DNA methylation and gene expression levels in whole blood of healthy human subjects. BMC Genomics. 2012;13:636. https://doi.org/10.1186/1471-2164-13-636.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  75. Wagner JR, Busche S, Ge B, Kwan T, Pastinen T, Blanchette M. The relationship between DNA methylation, genetic and expression inter-individual variation in untransformed human fibroblasts. Genome Biol. 2014;15(2):R37. https://doi.org/10.1186/gb-2014-15-2-r37.

    Article  PubMed Central  PubMed  Google Scholar 

  76. Lambrecht BN, Hammad H. The airway epithelium in asthma. Nat Med. 2012;18(5):684–92. https://doi.org/10.1038/nm.2737.

    Article  PubMed  CAS  Google Scholar 

  77. Lambrecht BN, Hammad H. Allergens and the airway epithelium response: Gateway to allergic sensitization. J Allergy Clin Immunol. 2014;134(3):499–507. https://doi.org/10.1016/j.jaci.2014.06.036.

    Article  PubMed  CAS  Google Scholar 

  78. Morales E, Bustamante M, Vilahur N, Escaramis G, Montfort M, de Cid R, Garcia-Esteban R, Torrent M, Estivill X, Grimalt JO, Sunyer J. DNA hypomethylation at ALOX12 is associated with persistent wheezing in childhood. Am J Respir Crit Care Med. 2012;185(9):937–43. https://doi.org/10.1164/rccm.201105-0870OC.

    Article  PubMed  CAS  Google Scholar 

  79. Acevedo N, Reinius LE, Greco D, Gref A, Orsmark-Pietras C, Persson H, Pershagen G, Hedlin G, Melen E, Scheynius A, Kere J, Soderhall C. Risk of childhood asthma is associated with CpG-site polymorphisms, regional DNA methylation and mRNA levels at the GSDMB/ORMDL3 locus. Hum Mol Genet. 2015;24(3):875–90. https://doi.org/10.1093/hmg/ddu479.

    Article  PubMed  CAS  Google Scholar 

  80. Yang IV, Pedersen BS, Liu A, O’Connor GT, Teach SJ, Kattan M, Misiak RT, Gruchalla R, Steinbach SF, Szefler SJ, Gill MA, Calatroni A, David G, Hennessy CE, Davidson EJ, Zhang W, Gergen P, Togias A, Busse WW, Schwartz DA. DNA methylation and childhood asthma in the inner city. J Allergy Clin Immunol. 2015;136(1):69–80. https://doi.org/10.1016/j.jaci.2015.01.025.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  81. Brunst KJ, Leung YK, Ryan PH, Khurana Hershey GK, Levin L, Ji H, Lemasters GK, Ho SM. Forkhead box protein 3 (FOXP3) hypermethylation is associated with diesel exhaust exposure and risk for childhood asthma. J Allergy Clin Immunol 2013;131(2):592–4 e591-3. doi:https://doi.org/10.1016/j.jaci.2012.10.042.

    Article  Google Scholar 

  82. Chen W, Boutaoui N, Brehm JM, Han YY, Schmitz C, Cressley A, Acosta-Perez E, Alvarez M, Colon-Semidey A, Baccarelli AA, Weeks DE, Kolls JK, Canino G, Celedon JC. ADCYAP1R1 and asthma in Puerto Rican children. Am J Respir Crit Care Med. 2013;187(6):584–8. https://doi.org/10.1164/rccm.201210-1789OC.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  83. Rastogi D, Suzuki M, Greally JM. Differential epigenome-wide DNA methylation patterns in childhood obesity-associated asthma. Sci Rep. 2013;3:2164. https://doi.org/10.1038/srep02164.

    Article  PubMed Central  PubMed  Google Scholar 

  84. Stefanowicz D, Hackett TL, Garmaroudi FS, Gunther OP, Neumann S, Sutanto EN, Ling KM, Kobor MS, Kicic A, Stick SM, Pare PD, Knight DA. DNA methylation profiles of airway epithelial cells and PBMCs from healthy, atopic and asthmatic children. PLoS One. 2012;7(9):e44213. https://doi.org/10.1371/journal.pone.0044213.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  85. Somineni HK, Zhang X, Biagini Myers JM, Kovacic MB, Ulm A, Jurcak N, Ryan PH, Khurana Hershey GK, Ji H. Ten-eleven translocation 1 (TET1) methylation is associated with childhood asthma and traffic-related air pollution. J Allergy Clin Immunol. 2016;137(3):797–805. e795. https://doi.org/10.1016/j.jaci.2015.10.021.

    Article  PubMed  CAS  Google Scholar 

  86. Yang IV, Pedersen BS, Liu AH, O’Connor GT, Pillai D, Kattan M, Misiak RT, Gruchalla R, Szefler SJ, Khurana Hershey GK, Kercsmar C, Richards A, Stevens AD, Kolakowski CA, Makhija M, Sorkness CA, Krouse RZ, Visness C, Davidson EJ, Hennessy CE, Martin RJ, Togias A, Busse WW, Schwartz DA. The nasal methylome and childhood atopic asthma. J Allergy Clin Immunol. 2016. https://doi.org/10.1016/j.jaci.2016.07.036.

  87. Yang IV, Richards A, Davidson EJ, Stevens AD, Kolakowski CA, Martin RJ, Schwartz DA. The nasal methylome: a key to understanding allergic asthma. Am J Respir Crit Care Med. 2017;195(6):829–31. https://doi.org/10.1164/rccm.201608-1558LE.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  88. Gunawardhana LP, Gibson PG, Simpson JL, Benton MC, Lea RA, Baines KJ. Characteristic DNA methylation profiles in peripheral blood monocytes are associated with inflammatory phenotypes of asthma. Epigenetics. 2014;9(9):1302–16. https://doi.org/10.4161/epi.33066.

    Article  PubMed Central  PubMed  Google Scholar 

  89. Nicodemus-Johnson J, Myers RA, Sakabe NJ, Sobreira DR, Hogarth DK, Naureckas ET, Sperling AI, Solway J, White SR, Nobrega MA, Nicolae DL, Gilad Y, Ober C. DNA methylation in lung cells is associated with asthma endotypes and genetic risk. JCI Insight. 2016;1(20):e90151. https://doi.org/10.1172/jci.insight.90151.

    Article  PubMed Central  PubMed  Google Scholar 

  90. Gilmour DS, Lis JT. Detecting protein-DNA interactions in vivo: distribution of RNA polymerase on specific bacterial genes. Proc Natl Acad Sci U S A. 1984;81(14):4275–9.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  91. O’Neill LP, Turner BM. Immunoprecipitation of native chromatin: NChIP. Methods. 2003;31(1):76–82.

    Article  PubMed  CAS  Google Scholar 

  92. Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, Wei G, Chepelev I, Zhao K. High-resolution profiling of histone methylations in the human genome. Cell. 2007;129(4):823–37. https://doi.org/10.1016/j.cell.2007.05.009.

    Article  PubMed  CAS  Google Scholar 

  93. Hitchler MJ, Rice JC. Genome-wide epigenetic analysis of human pluripotent stem cells by ChIP and ChIP-Seq. Methods Mol Biol. 2011;767:253–67. https://doi.org/10.1007/978-1-61779-201-4_19.

    Article  PubMed  CAS  Google Scholar 

  94. Straub T, Zabel A, Gilfillan GD, Feller C, Becker PB. Different chromatin interfaces of the Drosophila dosage compensation complex revealed by high-shear ChIP-seq. Genome Res. 2013;23(3):473–85. https://doi.org/10.1101/gr.146407.112.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  95. Brind’Amour J, Liu S, Hudson M, Chen C, Karimi MM, Lorincz MC. An ultra-low-input native ChIP-seq protocol for genome-wide profiling of rare cell populations. Nat Commun. 2015;6:6033. https://doi.org/10.1038/ncomms7033.

    Article  PubMed  CAS  Google Scholar 

  96. Stefanowicz D, Lee JY, Lee K, Shaheen F, Koo HK, Booth S, Knight DA, Hackett TL. Elevated H3K18 acetylation in airway epithelial cells of asthmatic subjects. Respir Res. 2015;16:95. https://doi.org/10.1186/s12931-015-0254-y.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  97. Harb H, Raedler D, Ballenberger N, Bock A, Kesper DA, Renz H, Schaub B. Childhood allergic asthma is associated with increased IL-13 and FOXP3 histone acetylation. J Allergy Clin Immunol. 2015;136(1):200–2. https://doi.org/10.1016/j.jaci.2015.01.027.

    Article  PubMed  CAS  Google Scholar 

  98. Prensner JR, Iyer MK, Balbin OA, Dhanasekaran SM, Cao Q, Brenner JC, Laxman B, Asangani IA, Grasso CS, Kominsky HD, Cao X, Jing X, Wang X, Siddiqui J, Wei JT, Robinson D, Iyer HK, Palanisamy N, Maher CA, Chinnaiyan AM. Transcriptome sequencing across a prostate cancer cohort identifies PCAT-1, an unannotated lincRNA implicated in disease progression. Nat Biotechnol. 2011;29(8):742–9. https://doi.org/10.1038/nbt.1914.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  99. Weikard R, Hadlich F, Kuehn C. Identification of novel transcripts and noncoding RNAs in bovine skin by deep next generation sequencing. BMC Genomics. 2013;14:789. https://doi.org/10.1186/1471-2164-14-789.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  100. Mestdagh P, Hartmann N, Baeriswyl L, Andreasen D, Bernard N, Chen C, Cheo D, D’Andrade P, DeMayo M, Dennis L, Derveaux S, Feng Y, Fulmer-Smentek S, Gerstmayer B, Gouffon J, Grimley C, Lader E, Lee KY, Luo S, Mouritzen P, Narayanan A, Patel S, Peiffer S, Ruberg S, Schroth G, Schuster D, Shaffer JM, Shelton EJ, Silveria S, Ulmanella U, Veeramachaneni V, Staedtler F, Peters T, Guettouche T, Wong L, Vandesompele J. Evaluation of quantitative miRNA expression platforms in the microRNA quality control (miRQC) study. Nat Methods. 2014;11(8):809–15. https://doi.org/10.1038/nmeth.3014.

    Article  PubMed  CAS  Google Scholar 

  101. Solberg OD, Ostrin EJ, Love MI, Peng JC, Bhakta NR, Hou L, Nguyen C, Solon M, Nguyen C, Barczak AJ, Zlock LT, Blagev DP, Finkbeiner WE, Ansel KM, Arron JR, Erle DJ, Woodruff PG. Airway epithelial miRNA expression is altered in asthma. Am J Respir Crit Care Med. 2012;186(10):965–74. https://doi.org/10.1164/rccm.201201-0027OC.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  102. Elbehidy RM, Youssef DM, El-Shal AS, Shalaby SM, Sherbiny HS, Sherief LM, Akeel NE. MicroRNA-21 as a novel biomarker in diagnosis and response to therapy in asthmatic children. Mol Immunol. 2016;71:107–14. https://doi.org/10.1016/j.molimm.2015.12.015.

    Article  PubMed  CAS  Google Scholar 

  103. Wang Y, Yang L, Li P, Huang H, Liu T, He H, Lin Z, Jiang Y, Ren N, Wu B, Kamp DW, Tan J, Liu G. Circulating microRNA signatures associated with childhood asthma. Clin Lab. 2015;61(5–6):467–74.

    PubMed  Google Scholar 

  104. Midyat L, Gulen F, Karaca E, Ozkinay F, Tanac R, Demir E, Cogulu O, Aslan A, Ozkinay C, Onay H, Atasever M. MicroRNA expression profiling in children with different asthma phenotypes. Pediatr Pulmonol. 2016;51(6):582–7. https://doi.org/10.1002/ppul.23331.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Asthma Research, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Hong Ji

  2. Pyrosequencing Lab for Genomic and Epigenomic Research, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Hong Ji

  3. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    Hong Ji

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  1. Zhongshan Hospital Institute of Clinical Science, Shanghai Medical School Fudan University, Shanghai, China

    Xiangdong Wang

  2. Shanghai Respiratory Research Institute, Respiratory Division of Zhongshan Hospital, Fudan University, Shanghai, China

    Zhihong Chen

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Ji, H. (2018). Epigenetics and Epigenomic Studies in Asthma. In: Wang, X., Chen, Z. (eds) Genomic Approach to Asthma. Translational Bioinformatics, vol 12. Springer, Singapore. https://doi.org/10.1007/978-981-10-8764-6_5

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