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Review

Epigenome-Modifying Tools in Asthma

, , &
Pages 1017-1032 | Published online: 07 Oct 2015

References

  • Masoli M , FabianD , HoltS , BeasleyR . The global burden of asthma: executive summary of the GINA Dissemination Committee Report . Allergy59 , 469 – 478 ( 2004 ).
  • WHO . Global surveillance, prevention and control of chronic respiratory diseases: a comprehensive approach . www.who.int/gard/publications/GARD%20Book%202007.pdf .
  • Bradding P , GreenRH . Subclinical phenotypes of asthma . Curr. Opin. Allergy Clin. Immunol.10 ( 1 ), 54 – 59 ( 2010 ).
  • Chung KF , WenzelSE , BrozekJLet al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma . Eur. Respir. J.43 ( 2 ), 343 – 373 ( 2014 ).
  • British Thoracic Society . British guideline on the management of asthma . Thorax69 ( Suppl. 1 ), 1 – 192 ( 2014 ).
  • Owen JA , PuntJ , StranfordSA , JonesPP . Kuby Immunology . W. H. Freeman and Company , New York, NY, USA ( 2007 ).
  • Bottcher MF , BjurstromJ , MaiX-M , NilssonL , JenmalmMC . Allergen-induced cytokine secretion in atopic and non atopic asthmatic children . Pediatr. Allergy Immunol. ( 14 ), 345 – 350 ( 2003 ).
  • Nurse B , PutermanAS , HausM , BermanD , WeinbergEG , PotterPC . PBMCs from both atopic asthmatic and nonatopic children show a T(H)2 cytokine response to house dust mite allergen . J. Allergy Clin. Immunol.106 , 84 – 91 ( 2000 ).
  • Woodruff PG , ModrekB , ChoyDFet al. T-helper type 2-driven inflammation defines major subphenotypes of asthma . Am. J. Respir. Crit. Care Med.180 ( 5 ), 388 – 395 ( 2009 ).
  • Langrish CL , ChenY , BlumenscheinWMet al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation . J. Exp. Med.201 ( 2 ), 233 – 240 ( 2005 ).
  • Al-Ramli W , PréfontaineD , ChouialiFet al. TH17-associated cytokines (IL-17A and IL-17F) in severe asthma . J. Allergy Clin. Immunol.123 ( 5 ), 1185 – 1187 ( 2009 ).
  • Oren R , Hod-MarcoM , Haus-CohenMet al. Thymus and autoimmunity: production of CD25+CD4+ naturally anergic and suppressive T cells as a key function of the thymus in maintaining immunologic self-tolerance . J. Immunol.193 , 5317 – 5326 ( 1999 ).
  • Zhou L , LopesJE , ChongMMWet al. TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function . Nature453 , 236 – 240 ( 2008 ).
  • Shi YH , ShiGC , WanHYet al. Coexistence of Th1/Th2 and Th17/Treg imbalances in patients with allergic asthma . Chin. Med. J. (Engl)124 , 1951 – 1956 ( 2011 ).
  • Thomsen SF , Van Der SluisS , KyvikKO , SkyttheA , BackerV . Estimates of asthma heritability in a large twin sample . Clin. Exp. Allergy40 , 1054 – 1061 ( 2010 ).
  • McGeachie MJ , StahlEA , HimesBEet al. Polygenic heritability estimates in pharmacogenetics: focus on asthma and related phenotypes . Pharmacogenet. Genomics23 ( 6 ), 324 – 328 ( 2013 ).
  • Woodruff PG , BousheyHA , DolganovGMet al. Genome-wide profiling identifies epithelial cell genes associated with asthma and with treatment response to corticosteroids . Proc. Natl Acad. Sci. USA104 ( 40 ), 1558 – 1563 ( 2007 ).
  • Moffatt M , GutI , DemenaisFet al. A large-scale, consortium-based genomewide association study of asthma . N. Engl. J. Med.363 ( 13 ), 1211 – 1221 ( 2010 ).
  • Durham AL , WiegmanC , AdcockIM . Epigenetics of asthma . Biochim. Biophys. Acta.1810 ( 11 ), 1103 – 1109 ( 2011 ).
  • Gunawardhana LP , GibsonPG , SimpsonJL , BentonMC , LeaRA , BainesKJ . Characteristic DNA methylation profiles in peripheral blood monocytes are associated with inflammatory phenotypes of asthma . Epigenetics9 ( 9 ), 1302 – 1316 ( 2014 ).
  • Rastogi D , SuzukiM , GreallyJM . Differential epigenome-wide DNA methylation patterns in childhood obesity-associated asthma . Sci. Rep.3 ( Table 1 ), 2164 ( 2013 ).
  • Zhang H , TongX , HollowayJWet al. The interplay of DNA methylation over time with Th2 pathway genetic variants on asthma risk and temporal asthma transition . Clin. Epigenetics6 , 8 ( 2014 ).
  • Liang L , Willis-OwenSAG , LapriseCet al. An epigenome-wide association study of total serum immunoglobulin E concentration . Nature520 ( 7549 ), 670 – 674 ( 2015 ).
  • Seumois G , ChavezL , GerasimovaAet al. Epigenomic analysis of primary human T cells reveals enhancers associated with TH2 memory cell differentiation and asthma susceptibility . Nat. Immunol.15 ( 8 ), 777 – 788 ( 2014 ).
  • Gerasimova A , ChavezL , LiBet al. Predicting cell types and genetic variations contributing to disease by combining GWAS and epigenetic data . PLoS ONE8 ( 1 ), e54359 ( 2013 ).
  • Wei G , WeiL , ZhuJet al. Global mapping of H3K4me3 and H3K27me3 reveals specificity and plasticity in lineage fate determination of differentiating CD4+ T cells . Immunity30 ( 1 ), 155 – 167 ( 2009 ).
  • Himes BE , JiangX , WagnerPet al. RNA-Seq transcriptome profiling identifies CRISPLD2 as a glucocorticoid responsive gene that modulates cytokine function in airway smooth muscle cells . PLoS ONE9 ( 6 ), e99625 ( 2014 ).
  • Pagdin T , LavenderP . MicroRNAs in lung diseases . Thorax67 , 183 – 184 ( 2012 ).
  • Clifford RL , PatelJK , JohnAEet al. CXCL8 Histone H3 acetylation is dysfunctional in airway smooth muscle in asthma: regulation by BET . Am. J. Physiol. - Lung Cell. Mol. Physiol. doi:10.1152/ajplung.00021.2015 ( 2015 ) ( Epub ahead of print ).
  • Thurman RE , RynesE , HumbertRet al. The accessible chromatin landscape of the human genome . Nature489 ( 7414 ), 75 – 82 ( 2012 ).
  • Kwon N-H , KimJ-S , LeeJ-Y , OhM-J , ChoiD-C . DNA methylation and the expression of IL-4 and IFN-gamma promoter genes in patients with bronchial asthma . J. Clin. Immunol.28 ( 2 ), 139 – 146 ( 2008 ).
  • Zafra MP , MazzeoC , GámezCet al. Gene silencing of SOCS3 by siRNA intranasal delivery inhibits asthma phenotype in mice . PLoS ONE9 ( 3 ), e91996 ( 2014 ).
  • Consortium RE , KundajeA , MeulemanWet al. Integrative analysis of 111 reference human epigenomes . Nature518 , 317 – 330 ( 2015 ).
  • ENCODE: Encyclopedia of DNA Elements . www.encodeproject.org/ .
  • Roadmap Epigenomics Project . www.roadmapepigenomics.org/ .
  • Romanoski CE , GlassCK , StunnenbergHG , WilsonL , AlmouzniG . Epigenomics: roadmap for regulation . Nature518 ( 7539 ), 314 – 316 ( 2015 ).
  • Dunham I , KundajeA , AldredSFet al. An integrated encyclopedia of DNA elements in the human genome . Nature489 ( 7414 ), 57 – 74 ( 2012 ).
  • Ransom M , DenneheyB , TylerJ . Chaperoning histones during DNA replication and repair . Cell140 ( 2 ), 183 – 195 ( 2010 ).
  • Luger K , MäderA , RichmondR . Crystal structure of the nucleosome core particle at 2.8 Å resolution . Nature7 , 251 – 260 ( 1997 ).
  • Ito K , YamamuraS , Essilfie-QuayeSet al. Histone deacetylase 2-mediated deacetylation of the glucocorticoid receptor enables NF-kappaB suppression . J. Exp. Med.203 ( 1 ), 7 – 13 ( 2006 ).
  • Vollmuth F , GeyerM . Interaction of propionylated and butyrylated histone H3 lysine marks with Brd4 bromodomains . Angew. Chem. Int. Ed. Engl.49 ( 38 ), 6768 – 6772 ( 2010 ).
  • Huisinga KL , Brower-TolandB , ElginSCR . The contradictory definitions of heterochromatin: transcription and silencing . Chromosoma115 ( 2 ), 110 – 122 ( 2006 ).
  • Tessarz P , KouzaridesT . Histone core modifications regulating nucleosome structure and dynamics . Nat. Rev. Mol. Cell Biol.15 ( 11 ), 703 – 708 ( 2014 ).
  • Dumuis-Kervabon A , EncontreI , EtienneGet al. A chromatin core particle obtained by selective cleavage of histones by clostripain . EMBO J.5 ( 7 ), 1735 – 1742 ( 1986 ).
  • Xu WS , ParmigianiRB , MarksPA . Histone deacetylase inhibitors: molecular mechanisms of action . Oncogene.26 , 5541 – 5552 ( 2007 ).
  • Portela A , EstellerM . Epigenetic modifications and human disease . Nat. Biotechnol.28 ( 10 ), 1057 – 1068 ( 2010 ).
  • Ito K , CaramoriG , LimSet al. Expression and activity of histone deacetylases in human asthmatic airways . Am. J. Respir. Crit. Care Med.166 , 392 – 396 ( 2002 ).
  • Su R-C , BeckerAB , KozyrskyjAL , HayglassKT . Epigenetic regulation of established human type 1 versus type 2 cytokine responses . J. Allergy Clin. Immunol.121 , 57 – 63.e3 ( 2008 ).
  • Creyghton MP , ChengAW , WelsteadGGet al. Histone H3K27ac separates active from poised enhancers and predicts developmental state . Proc. Natl Acad. Sci. USA107 ( 50 ), 21931 – 21936 ( 2010 ).
  • Vijayanand P , SeumoisG , SimpsonLJet al. Interleukin-4 production by follicular helper T cells requires the conserved IL-4 enhancer Hypersensitivity Site V . Immunity36 ( 2 ), 175 – 187 ( 2012 ).
  • Yu Q , ZhouB , ZhangYet al. DNA methyltransferase 3a limits the expression of interleukin-13 in T helper 2 cells and allergic airway inflammation . Proc. Natl Acad. Sci.109 , 541 – 546 ( 2012 ).
  • Imhof A , FellerC , ForneI , BeckerPB , ImhofA , BeckerPB . Global and specific responses of the histone acetylome to systematic perturbation resource global and specific responses of the histone acetylome to systematic perturbation . Mol. Cell57 ( 3 ), 559 – 571 ( 2015 ).
  • Chen L , FischleW , VerdinE , GreeneW . Duration of nuclear NF-κB action regulated by reversible acetylation . Science293 ( 5535 ), 1653 – 1657 ( 2001 ).
  • Marwick J a , CaramoriG , StevensonCSet al. Inhibition of PI3Kdelta restores glucocorticoid function in smoking-induced airway inflammation in mice . Am. J. Respir. Crit. Care Med.179 ( 7 ), 542 – 548 ( 2009 ).
  • Wang Y , TianY , MorleyM , LuM . Development and regeneration of Sox2+ endoderm progenitors are regulated by a Hdac1/2-Bmp4/Rb1 regulatory pathway . Dev. Cell.24 ( 4 ), 345 – 358 ( 2013 ).
  • Chetta A , ForesiA , Del DonnoM , BertorelliG , PesciA , OlivieriD . Airways remodeling is a distinctive feature of asthma and is related to severity of disease . Chest111 , 852 – 857 ( 1997 ).
  • Butler CA , McQuaidS , TaggartCCet al. Glucocorticoid receptor β and histone deacetylase 1 and 2 expression in the airways of severe asthma . Thorax67 ( 5 ), 392 – 398 ( 2012 ).
  • Belkina AC , NikolajczykBS , DenisGV . BET protein function is required for inflammation: Brd2 genetic disruption and BET inhibitor JQ1 impair mouse macrophage inflammatory responses . J. Immunol.190 ( 7 ), 3670 – 3678 ( 2013 ).
  • Huang B , YangX-D , ZhouM-M , OzatoK , ChenL-F . Brd4 coactivates transcriptional activation of NF-kappaB via specific binding to acetylated RelA . Mol. Cell. Biol.29 ( 5 ), 1375 – 1387 ( 2009 ).
  • Wu S-Y , ChiangC-M . The double bromodomain-containing chromatin adaptor Brd4 and transcriptional regulation . J. Biol. Chem.282 ( 18 ), 13141 – 13145 ( 2007 ).
  • Royce S . Histone deacetylase inhibitors: can we consider potent anti-neoplastic agents for the treatment of asthma?Ann. Clin. Lab. Sci.42 ( 3 ), 338 – 345 ( 2012 ).
  • Hou X , WanH , AiXet al. Histone deacetylase inhibitor regulates the balance of Th17/Treg in allergic asthma . Clin. Respir. J. doi:10.1111/crj.12227 ( 2014 ) ( Epub ahead of print ).
  • Choi SW , GatzaE , HouGet al. Histone deacetylase inhibition regulates inflammation and enhances Tregs after allogeneic hematopoietic cell transplantation in humans . Blood125 ( 5 ), 815 – 819 ( 2014 ).
  • Cheng Z , GongY , MaYet al. Inhibition of BET bromodomain targets genetically diverse glioblastoma . Clin. Cancer Res.19 , 1748 – 1759 ( 2013 ).
  • Delmore JE , IssaGC , LemieuxMEet al. BET bromodomain inhibition as a therapeutic strategy to target c-Myc . Cell146 ( 6 ), 904 – 917 ( 2011 ).
  • Lewis MD , MillerSA , MiazgowiczMM , BeimaKM , WeinmannAS . T-bet’s ability to regulate individual target genes requires the conserved T-box domain to recruit histone methyltransferase activity and a separate family member-specific transactivation domain . Mol. Cell. Biol.27 ( 24 ), 8510 – 8521 ( 2007 ).
  • Rai G , KawamuraA , Anthony TumberYLet al. ML324, a JMJD2 demethylase inhibitor with demonstrated antiviral activity . In : Probe Reports from the NIH Molecular Libraries Program . National Center for Biotechnology Information , MD, USA ( 2013 ).
  • Kruidenier L , ChungC , ChengZet al. A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response . Nature488 ( 7411 ), 404 – 408 ( 2012 ).
  • Prusevich P , KalinJ , MingS . A selective phenelzine analogue inhibitor of histone demethylase LSD1 . ACS Chem. Biol.9 ( 6 ), 1284 – 1293 ( 2014 ).
  • Brand S , KesperDA , TeichRet al. DNA methylation of TH1/TH2 cytokine genes affects sensitization and progress of experimental asthma . J. Allergy Clin. Immunol.129 ( 6 ), 1602 – 1610.e6 ( 2012 ).
  • Cheray M , NadaradjaneA , BonnetP , RoutierS , ValletteFM , CartronP-F . Specific inhibition of DNMT1/CFP1 reduces cancer phenotypes and enhances chemotherapy effectiveness . Epigenomics6 ( 3 ), 267 – 275 ( 2014 ).
  • Ling H , FabbriM , CalinGA . MicroRNAs and other non-coding RNAs as targets for anticancer drug development . Nat. Rev. Drug Discov.12 , 847 – 865 ( 2013 ).
  • Janssen HLA , ReesinkHW , LawitzEJet al. Treatment of HCV infection by targeting microRNA . N. Engl. J. Med.368 , 1685 – 1694 ( 2013 ).
  • Bryniarski K , PtakW , JayakumarAet al. Antigen-specific, antibody-coated, exosome-like nanovesicles deliver suppressor T-cell microRNA-150 to effector T cells to inhibit contact sensitivity . J. Allergy Clin. Immunol.132 ( 1 ), 170 – 181 ( 2013 ).
  • Li JJ , TayHL , MaltbySet al. MicroRNA-9 regulates steroid-resistant airway hyperresponsiveness by reducing protein phosphatase 2A activity . J. Allergy Clin. Immunol.136 ( 2 ), 462 – 473 ( 2015 ).
  • Collison A , MattesJ , PlankM , FosterPS . Inhibition of house dust mite-induced allergic airways disease by antagonism of microRNA-145 is comparable to glucocorticoid treatment . J. Allergy Clin. Immunol.128 ( 1 ), 160 – 167 ( 2011 ).
  • Mattes J , CollisonA , PlankM , PhippsS , FosterPS . Antagonism of microRNA-126 suppresses the effector function of TH2 cells and the development of allergic airways disease . Proc. Natl Acad. Sci. USA106 ( 44 ), 18704 – 18709 ( 2009 ).
  • Banerjee A , TrivediCM , DameraGet al. Trichostatin A abrogates airway constriction, but not inflammation, in murine and human asthma models . Am. J. Respir. Cell Mol. Biol.46 ( 2 ), 132 – 138 ( 2012 ).
  • Kim Y , KimK , ParkDet al. Histone deacetylase 3 mediates allergic skin inflammation by regulating expression of MCP1 protein . J. Biol. Chem.287 ( 31 ), 25844 – 25859 ( 2012 ).
  • Kienzler A-K , RizziM , ReithM , NuttSL , EibelH . Inhibition of human B-cell development into plasmablasts by histone deacetylase inhibitor valproic acid . J. Allergy Clin. Immunol.131 ( 6 ), 1695 – 1699 ( 2013 ).
  • Shi YL , GuJ , ParkJYet al. Histone deacetylases inhibitor Trichostatin A ameliorates DNFB-induced allergic contact dermatitis and reduces epidermal Langerhans cells in mice . J. Dermatol. Sci.68 ( 2 ), 99 – 107 ( 2012 ).
  • Barnes PJ . Theophylline . Am. J. Respir. Crit. Care Med.188 ( 5 ), 901 – 906 ( 2013 ).
  • Ford PA , DurhamAL , RussellREK , GordonF , AdcockIM , BarnesPJ . Treatment effects of low-dose theophylline combined with an inhaled corticosteroid in COPD . Chest.137 , 1338 – 1344 ( 2010 ).
  • Barnes P , AdcockI , ItoK . Histone acetylation and deacetylation: importance in inflammatory lung diseases . Eur. Respir. J.25 ( 3 ), 552 – 563 ( 2005 ).
  • Pinz S , UnserS , BuobD , FischerP , JobstB , RascleA . Deacetylase inhibitors repress STAT5-mediated transcription by interfering with bromodomain and extra-terminal (BET) protein function . Nucleic Acids Res.43 ( 7 ), 3524 – 3545 ( 2015 ).
  • Royce SG , KaragiannisTC . Histone deacetylases and their inhibitors: new implications for asthma and chronic respiratory conditions . Curr. Opin. Allergy Clin. Immunol.14 ( 1 ), 44 – 8 ( 2014 ).
  • Hakim A , AdcockI , UsmaniO . Corticosteroid resistance and novel anti-inflammatory therapies in chronic obstructive pulmonary disease . Drugs72 ( 10 ), 1299 – 1312 ( 2012 ).
  • Heller EA , CatesHM , PeñaCJet al. Locus-specific epigenetic remodeling controls addiction- and depression-related behaviors . Nat. Neurosci.17 ( 12 ), 1720 – 1727 ( 2014 ).
  • Konermann S , BrighamMD , TrevinoAEet al. Optical control of mammalian endogenous transcription and epigenetic states . Nature500 ( 7463 ), 472 – 476 ( 2013 ).
  • Berkovits BD , WolgemuthDJ . The role of the double bromodomain-containing BET genes during mammalian spermatogenesis . Curr. Top. Dev. Biol.102 , 293 – 326 ( 2013 ).
  • Moon KJ , MochizukiK , ZhouM , JeongHS , BradyJN , OzatoK . The bromodomain protein Brd4 is a positive regulatory component of P-TEFb and stimulates RNA polymerase II-dependent transcription . Mol. Cell.19 , 523 – 534 ( 2005 ).
  • Zeng L , ZhouMM . Bromodomain: an acetyl-lysine binding domain . FEBS Lett.513 ( 1 ), 124 – 128 ( 2002 ).
  • Wu SY , LeeAY , HouSYet al. Brd4 links chromatin targeting to HPV transcriptional silencing . Genes Dev.20 , 2383 – 2396 ( 2006 ).
  • Filippakopoulos P , QiJ , PicaudSet al. Selective inhibition of BET bromodomains . Nature468 ( 7327 ), 1067 – 1073 ( 2010 ).
  • Khan YM , KirkhamP , BarnesPJ , AdcockIM . Brd4 is essential for IL-1B-induced inflammation in human airway epithelial cells . PLoS ONE9 ( 4 ), 1 – 17 ( 2014 ).
  • Perry MM , DurhamAL , AustinPJ , AdcockIM , ChungKF . BET bromodomains regulate TGF-β-induced proliferation and cytokine release in asthmatic airway smooth muscle . J. Biol. Chem.290 ( 14 ), 9111 – 9121 ( 2015 ).
  • Simon JA , LangeCA . Roles of the EZH2 histone methyltransferase in cancer epigenetics . Mutat. Res.647 ( 1–2 ), 21 – 29 ( 2008 ).
  • Koche RP , SmithZD , AdliMet al. Reprogramming factor expression induces rapid and widespread targeted chromatin remodeling . Cell Stem Cell.8 ( 1 ), 96 – 105 ( 2011 ).
  • Ansel KM , DjureticI , TanasaB , RaoA . Regulation of Th2 differentiation and IL-4 locus accessibility . Annu. Rev. Immunol.24 , 607 – 656 ( 2006 ).
  • Ernst J , KheradpourP , MikkelsenTSet al. Mapping and analysis of chromatin state dynamics in nine human cell types . Nature473 ( 7345 ), 43 – 49 ( 2011 ).
  • Perros F , HoogstedenHC , CoyleAJ , LambrechtBN , HammadH . Blockade of CCR4 in a humanized model of asthma reveals a critical role for DC-derived CCL17 and CCL22 in attracting Th2 cells and inducing airway inflammation . Allergy64 ( 7 ), 995 – 1002 ( 2009 ).
  • Chan O , BurkeJD , GaoDF , FishEN . The chemokine CCL5 regulates glucose uptake and AMP kinase signaling in activated T cells to facilitate chemotaxis . J. Biol. Chem.287 ( 35 ), 29406 – 29416 ( 2012 ).
  • Barsyte-Lovejoy D , LiF , OudhoffMJet al. (R)-PFI-2 is a potent and selective inhibitor of SETD7 methyltransferase activity in cells . Proc. Natl Acad. Sci. USA111 ( 35 ), 12853 – 12858 ( 2014 ).
  • Wang H , CaoR , XiaLet al. Purification and functional characterization of a histone H3-lysine 4-specific methyltransferase . Mol. Cell.8 , 1207 – 1217 ( 2001 ).
  • Zhu Y , van EssenD , SaccaniS . Cell-type-specific control of enhancer activity by H3K9 trimethylation . Mol. Cell.46 ( 4 ), 408 – 423 ( 2012 ).
  • Clifford RL , JohnAE , BrightlingCE , KnoxAJ . Abnormal histone methylation is responsible for increased VEGF165a secretion from airway smooth muscle cells in asthma . J. Immunol.189 ( 2 ), 819 – 831 ( 2012 ).
  • Whetstine JR , NottkeA , LanFet al. Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases . Cell125 ( 3 ), 467 – 481 ( 2006 ).
  • Liu F , Barsyte-LovejoyD , LiFet al. Discovery of an in vivo chemical probe of the lysine methyltransferases G9a and GLP . J. Med. Chem.56 ( 21 ), 8931 – 8942 ( 2013 ).
  • Tachibana M , SugimotoK , NozakiMet al. G9a histone methyltransferase plays a dominant role in euchromatic histone H3 lysine 9 methylation and is essential for early embryogenesis . Genes Dev.16 , 1779 – 1791 ( 2002 ).
  • Young MD , WillsonTA , WakefieldMJet al. ChIP-seq analysis reveals distinct H3K27me3 profiles that correlate with transcriptional activity . Nucleic Acids Res.39 ( 17 ), 7415 – 7427 ( 2011 ).
  • Tumes DJ , OnoderaA , SuzukiAet al. The polycomb protein Ezh2 regulates differentiation and plasticity of CD4(+) T helper type 1 and type 2 cells . Immunity39 ( 5 ), 819 – 832 ( 2013 ).
  • Miller S , MohnS , WeinmannA . Jmjd3 and UTX play a demethylase-independent role in chromatin remodeling to regulate T-box family member- dependent gene expression . Mol. Cell.40 ( 4 ), 594 – 605 ( 2010 ).
  • Xiang Y , ZhuZ , HanG , LinH , XuL , ChenCD . JMJD3 is a histone H3K27 demethylase . Cell Res.17 ( 10 ), 850 – 857 ( 2007 ).
  • Ishii M , WenH , CorsaCASet al. Epigenetic regulation of the alternatively activated macrophage phenotype . Blood114 ( 15 ), 3244 – 3254 ( 2009 ).
  • Satoh T , TakeuchiO , VandenbonAet al. The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection . Nat. Immunol.11 ( 10 ), 936 – 944 ( 2010 ).
  • Han H , XuD , LiuC , ClaessonH-E , BjörkholmM , SjöbergJ . Interleukin-4-mediated 15-lipoxygenase-1 trans-activation requires UTX recruitment and H3K27me3 demethylation at the promoter in A549 cells . PLoS ONE9 ( 1 ), e85085 ( 2014 ).
  • Kuperman DA , LewisCC , WoodruffPGet al. Dissecting asthma using focused transgenic modeling and functional genomics . J. Allergy Clin. Immunol.116 ( 2 ), 305 – 311 ( 2005 ).
  • Vianello P , BotrugnoOA , CappaAet al. Synthesis, biological activity and mechanistic insights of 1-substituted cyclopropylamine derivatives: a novel class of irreversible inhibitors of histone demethylase KDM1A . Eur. J. Med. Chem.86 , 352 – 363 ( 2014 ).
  • Law JA , JacobsenSE . Establishing, maintaining and modifying DNA methylation patterns in plants and animals . Nat. Rev. Genet.11 ( 3 ), 204 – 220 ( 2010 ).
  • Hermann A , GoyalR , JeltschA . The Dnmt1 DNA-(cytosine-C5)-methyltransferase methylates DNA processively with high preference for hemimethylated target sites . J. Biol. Chem.279 ( 46 ), 48350 – 48359 ( 2004 ).
  • Williams CL , SchillingMM , ChoSHet al. STAT4 and T-bet are required for the plasticity of IFN-γ expression across Th2 ontogeny and influence changes in Ifng promoter DNA methylation1 . J. Immunol.191 ( 2 ), 678 – 687 ( 2013 ).
  • Verma M , ChattopadhyayBD , PaulBN . Epigenetic regulation of DNMT1 gene in mouse model of asthma disease . Mol. Biol. Rep.40 ( 3 ), 2357 – 2368 ( 2013 ).
  • Rai K , JafriIF , ChidesterSet al. Dnmt3 and G9a cooperate for tissue-specific development in zebrafish . J. Biol. Chem.285 ( 6 ), 4110 – 4121 ( 2010 ).
  • Yu D , WaterlandRA , ZhangPet al. Targeted p16Ink4a epimutation causes tumorigenesis and reduces survival in mice . J. Clin. Invest.124 ( 9 ), 3708 – 3712 ( 2014 ).
  • Di Ruscio A , EbralidzeAK , BenoukrafTet al. DNMT1-interacting RNAs block gene-specific DNA methylation . Nature503 ( 7476 ), 371 – 6 ( 2013 ).
  • Estève P , ChinH . Direct interaction between DNMT1 and G9a coordinates DNA and histone methylation during replication . Genes Dev.3089 – 3103 ( 2006 ).
  • Robertson K , Ait-Si-AliS , YokochiT . DNMT1 forms a complex with Rb, E2F1 and HDAC1 and represses transcription from E2F-responsive promoters . Nat. Genet.25 ( 3 ), 338 – 342 ( 2000 ).
  • Chuang L , IanH , KohT , NgH , XuG , LiB . Human DNA-(cytosine-5) methyltransferase-PCNA complex as a target for p21WAF1 . Science277 ( 5334 ), 80 ( 1997 ).
  • Booton R , LindsayMA . Emerging role of microRNAs and long noncoding RNAs in respiratory disease . Chest146 , 193 – 204 ( 2014 ).
  • Xu W , HuiC , YuSSB , JingC , ChanHC . MicroRNAs and cystic fibrosis‐‐an epigenetic perspective . Cell Biol. Int.35 , 463 – 466 ( 2011 ).
  • Yu JCC , MartinS , NasrJ , StaffordK , ThompsonD , PetrikovicsI . MicroRNAs in lung cancer . World J. Methodol.2 ( 2 ), 33 – 41 ( 2012 ).
  • Bartel DP . MicroRNAs: genomics, biogenesis, mechanism, and function . Cell116 , 281 – 297 ( 2004 ).
  • Friedman RC , FarhKKH , BurgeCB , BartelDP . Most mammalian mRNAs are conserved targets of microRNAs . Genome Res.19 , 92 – 105 ( 2009 ).
  • Perry MM , TsitsiouE , AustinPJet al. Role of non-coding RNAs in maintaining primary airway smooth muscle cells . Respir. Res.15 , 58 ( 2014 ).
  • Martinez-Nunez RT , BondaneseVP , LouafiFet al. A MicroRNA network dysregulated in asthma controls IL-6 production in bronchial epithelial cells . PLoS ONE9 ( 10 ), e111659 ( 2014 ).
  • Perry MM , BakerJE , GibeonDS , AdcockIM , ChungKF . Airway smooth muscle hyperproliferation is regulated by MicroRNA-221 in severe asthma . Am. J. Respir. Cell Mol. Biol.50 , 7 – 17 ( 2014 ).
  • Solberg OD , OstrinEJ , LoveMIet al. Airway epithelial miRNA expression is altered in asthma . Am. J. Respir. Crit. Care Med.186 ( 10 ), 965 – 974 ( 2012 ).
  • Takyar S , VasavadaH , ZhangJet al. VEGF controls lung Th2 inflammation via the miR-1-Mpl (myeloproliferative leukemia virus oncogene)-P-selectin axis . J. Exp. Med.210 , 1993 – 2010 ( 2013 ).
  • Asai-Tajiri Y , MatsumotoK , FukuyamaSet al. Small interfering RNA against CD86 during allergen challenge blocks experimental allergic asthma . Respir. Res.15 ( 1 ), 132 ( 2014 ).
  • Kakiuchi-Kiyota S , Koza-TaylorPH , MantenaSRet al. Comparison of hepatic transcription profiles of locked ribonucleic acid antisense oligonucleotides: evidence of distinct pathways contributing to non-target mediated toxicity in mice . Toxicol. Sci.138 , 234 – 248 ( 2014 ).
  • Gilleron J , QuerbesW , ZeigererAet al. Image-based analysis of lipid nanoparticle-mediated siRNA delivery, intracellular trafficking and endosomal escape . Nat. Biotechnol.31 , 638 – 646 ( 2013 ).
  • Jang SC , KimOY , YoonCMet al. Bioinspired exosome-mimetic nanovesicles for targeted delivery of chemotherapeutics to malignant tumors . ACS Nano.7 , 7698 – 7710 ( 2013 ).
  • Taulli R , LoretelliC , PandolfiP . From pseudo-ceRNAs to circ-ceRNAs: a tale of cross-talk and competition . Nat. Struct. Mol. Biol.20 ( 5 ), 541 – 543 ( 2013 ).
  • Cong L , RanF , CoxD , LinS , BarrettoR . Multiplex genome engineering using CRISPR/Cas systems . Science339 ( 6121 ), 819 – 823 ( 2013 ).