13
Views
0
CrossRef citations to date
0
Altmetric
Review

Epigenetics and stroke risk – beyond the static DNA code

, &
Pages 67-84 | Published online: 16 Oct 2012

References

  • Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics – 2012 update: a report from the American Heart Association. Circulation. 2012;125(1):e2–e220.
  • Heidenreich PA, Trogdon JG, Khavjou OA, et al. Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart Association. Circulation. 2011;123(8):933–944.
  • Di Carlo A. Human and economic burden of stroke. Age Ageing. 2009;38(1):4–5.
  • Strong K, Mathers C, Bonita R. Preventing stroke: saving lives around the world. Lancet Neurol. 2007;6(2):182–187.
  • Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJ. Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet. 2006;367(9524):1747–1757.
  • Johnston SC, Mendis S, Mathers CD. Global variation in stroke burden and mortality: estimates from monitoring, surveillance, and modelling. Lancet Neurol. 2009;8(4):345–354.
  • Feigin VL, Lawes CM, Bennett DA, Barker-Collo SL, Parag V Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic review. Lancet Neurol. 2009;8(4):355–369.
  • Warlow C, van Gijn J, Dennis M, et al. Stroke: Practical Management. 3rd ed. Oxford: Blackwell Publishing; 2008:39–40.
  • Adams HP Jr, Bendixen BH, Kappelle LJ, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993;24(1):35–41.
  • Meschia JF, Worrall BB, Rich SS. Genetic susceptibility to ischemic stroke. Nat Rev Neurol. 2011;7(7):369–378.
  • Lanktree MB, Dichgans M, Hegele RA. Advances in genomic analysis of stroke: what have we learned and where are we headed? Stroke. 2010;41(4):825–832.
  • Yan MS, Matouk CC, Marsden PA. Epigenetics ofthe vascular endothelium. J Appl Physiol. 2010;109(3):916–926.
  • Matouk CC, Marsden PA. Epigenetic regulation of vascular endothelial gene expression. Circ Res. 2008;102(8):873–887.
  • Shirodkar AV, Marsden PA. Epigenetics in cardiovascular disease. Curr Opin Cardiol. 2011;26(3):209–215.
  • Rubattu S, Volpe M, Kreutz R, Ganten U, Ganten D, Lindpaintner K. Chromosomal mapping of quantitative trait loci contributing to stroke in a rat model of complex human disease. Nat Genet. 1996;13(4):429–434.
  • Barone FC, Knudsen DJ, Nelson AH, Feuerstein GZ, Willette RN. Mouse strain differences in susceptibility to cerebral ischemia are related to cerebral vascular anatomy. J Cereb Blood Flow Metab. 1993;13(4):683–692.
  • Majid A, He YY, Gidday JM, et al. Differences in vulnerability to permanent focal cerebral ischemia among 3 common mouse strains. Stroke. 2000;31(11):2707–2714.
  • Lambertsen KL, Gregersen R, Finsen B. Microglial-macrophage synthesis of tumor necrosis factor after focal cerebral ischemia in mice is strain dependent. J Cereb Blood Flow Metab. 2002;22(7):785–797.
  • Keum S, Marchuk DA. A locus mapping to mouse chromosome 7 determines infarct volume in a mouse model of ischemic stroke. Circ Cardiovasc Genet. 2009;2(6):591–598.
  • Dichgans M. Genetics of ischaemic stroke. Lancet Neurol. 2007;6(2):149–161.
  • Seshadri S, Beiser A, Pikula A, et al. Parental occurrence of stroke and risk of stroke in their children: the Framingham study. Circulation. 2010;121(11):1304–1312.
  • Bevan S, Markus HS. Genetics of common polygenic ischaemic stroke: current understanding and future challenges. Stroke Res Treat. 2011;2011:179061.
  • Duggirala R, Gonzalez Villalpando C, O’ Leary DH, Stern MP Blangero J. Genetic basis of variation in carotid artery wall thickness. Stroke. 1996;27(5):833–837.
  • Moskau S, Golla A, Grothe C, Boes M, Pohl C, Klockgether T. Heritability of carotid artery atherosclerotic lesions: an ultrasound study in 154 families. Stroke. 2005;36(1):5–8.
  • Jartti L, Ronnemaa T, Kaprio J, et al. Population-based twin study of the effects of migration from Finland to Sweden on endothelial function and intima-media thickness. Arterioscler Thromb Vasc Biol. 2002;22(5):832–837.
  • Anderson CD, Biffi A, Rost NS, Cortellini L, Furie KL, Rosand J. Chromosome 9p21 in ischemic stroke: population structure and metaanalysis. Stroke. 2010;41(6):1123–1131.
  • Holdt LM, Teupser D. Recent studies of the human chromosome 9p21 locus, which is associated with atherosclerosis in human populations. Arterioscler Thromb Vasc Biol. 2012;32(2):196–206.
  • Bellenguez C, Bevan S, Gschwendtner A, et al. Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke. Nat Genet. 2012;44(3):328–333.
  • Holliday EG, Maguire JM, Evans TJ, et al. Common variants at 6p21.1 are associated with large artery atherosclerotic stroke. Nat Genet. 2012;44(10):1147–1151.
  • Noh KM, Hwang JY, Follenzi A, et al. Repressor element-1 silencing transcription factor (REST)-dependent epigenetic remodeling is critical to ischemia-induced neuronal death. Proc Natl Acad Sci US A. 2012;109(16):E962–E971.
  • Skowronski K, Dubey S, Rodenhiser D, Coomber B. Ischemia dysregulates DNA methyltransferases and p16INK4a methylation in human colorectal cancer cells. Epigenetics. 2010;5(6):547–556.
  • van Loo KM, Schaub C, Pernhorst K, et al. Transcriptional regulation of T-type calcium channel CaV3.2: bi-directionality by early growth response 1 (Egr1) and repressor element 1 (RE-1) protein-silencing transcription factor (REST). J Biol Chem. 2012;287(19):15489–15501.
  • Bithell A. REST: transcriptional and epigenetic regulator. Epigenomics. 2011;3(1):47–58.
  • Formisano L, Noh KM, Miyawaki T, Mashiko T, Bennett MV Zukin RS. Ischemic insults promote epigenetic reprogramming of mu opioid receptor expression in hippocampal neurons. Proc Natl Acad Sci U S A. 2007;104(10):4170–4175.
  • Grimm D, Streetz KL, Jopling CL, et al. Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Nature. 2006;441(7092):537–541.
  • Marsden PA. RNA interference as potential therapy – not so fast. N Engl J Med. 2006;355(9):953–954.
  • Martin L, Chang HY. Uncovering the role of genomic “dark matter” in human disease. J Clinical Invest. 2012;122(5):1589–1595.
  • Gupta RA, Shah N, Wang KC, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464(7291):1071–1076.
  • Petronis A. Epigenetics and twins: three variations on the theme. Trends Genet. 2006;22(7):347–350.
  • Poulsen P, Esteller M, Vaag A, Fraga MF. The epigenetic basis of twin discordance in age-related diseases. Pediatr Res. 2007;61(5 Pt 2): 38R–42R.
  • Bak S, Gaist D, Sindrup SH, Skytthe A, Christensen K. Genetic liability in stroke: a long-term follow-up study of Danish twins. Stroke. 2002;33(3):769–774.
  • Brass LM, Isaacsohn JL, Merikangas KR, Robinette CD. A study of twins and stroke. Stroke. 1992;23(2):221–223.
  • Chabriat H, Joutel A, Dichgans M, Tournier-Lasserve E, Bousser MG. Cadasil. Lancet Neurol. 2009;8(7):643–653.
  • Ayata C. CADASIL: experimental insights from animal models. Stroke. 2010;41(Suppl 10):S129–S134.
  • Dichgans M, Mayer M, Uttner I, et al. The phenotypic spectrum of CADASIL: clinical findings in 102 cases. Ann Neurol. 1998;44(5):731–739.
  • Opherk C, Peters N, Holtmannspotter M, Gschwendtner A, Muller-Myhsok B, Dichgans M. Heritability of MRI lesion volume in CADASIL: evidence for genetic modifiers. Stroke. 2006;37(11):2684–2689.
  • Adib-Samii P, Brice G, Martin RJ, Markus HS. Clinical spectrum of CADASIL and the effect of cardiovascular risk factors on phenotype: study in 200 consecutively recruited individuals. Stroke. 2010;41(4):630–634.
  • Mykkanen K, Junna M, Amberla K, et al. Different clinical phenotypes in monozygotic CADASIL twins with a novel NOTCH3 mutation. Stroke. 2009;40(6):2215–2218.
  • Mykkanen K, Savontaus ML, Juvonen V et al. Detection of the founder effect in Finnish CADASIL families. Eur J Hum Genet. 2004;12(10):813–819.
  • Hardy J, Singleton A. Genomewide association studies and human disease. N Engl J Med. 2009;360(17):1759–1768.
  • Manolio TA, Collins FS, Cox NJ, et al. Finding the missing heritability of complex diseases. Nature. 2009;461(7265):747–753.
  • Visscher PM. Sizing up human height variation. Nat Genet. 2008;40(5):489–490.
  • Perola M. Genetics of human stature: Lessons from genome-wide association studies. Horm Res Paediatr. 2011;76 Suppl 3:10–11.
  • Gibson G. Rare and common variants: twenty arguments. Nat Rev Genet. 2011;13(2):135–145.
  • Petronis A. Epigenetics as a unifying principle in the aetiology of complex traits and diseases. Nature. 2010;465(7299):721–727.
  • Yap KL, Li S, Munoz-Cabello AM, et al. Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a. Mol Cell. 2010;38(5):662–674.
  • Lanktree MB, Hegele RA, Yusuf S, Anand SS. Multi-ethnic genetic association study of carotid intima-media thickness using a targeted cardiovascular SNP microarray. Stroke. 2009;40(10):3173–3179.
  • Finishing the euchromatic sequence of the human genome. Nature. 2004;431(7011):931–945.
  • Chen S. Length of a human DNA molecule. 1998. Available from: http://hypertextbook.com/facts/1998/StevenChen.shtml. Accessed September 4, 2012.
  • van Holde K, Zlatanova J, Arents G, Moudrianakis E. Elements of chromatin structure: histones, nucleosomes, and fibres. In: Elgin SCR, editor. Chromtin Structure and Gene Expression. New York: IRL Press; 1995:1–26.
  • Miranda TB, Jones PA. DNA methylation: the nuts and bolts of repression. J Cell Physiol. 2007;213(2):384–390.
  • Bernstein BE, Meissner A, Lander ES. The mammalian epigenome. Cell. 2007;128(4):669–681.
  • Gardiner-Garden M, Frommer M. CpG islands in vertebrate genomes. J Mol Biol. 1987;196(2):261–282.
  • Takai D, Jones PA. Comprehensive analysis of CpG islands in human chromosomes 21 and 22. Proc Natl Acad Sci U S A. 2002;99(6):3740–3745.
  • Illingworth RS, Bird AP. CpG islands – ‘a rough guide’. FEBS Lett. 2009;583(11):1713–1720.
  • Law JA, Jacobsen SE. Establishing, maintaining and modifying DNA methylation patterns in plants and animals. Nat Rev Genet. 2010;11(3):204–220.
  • Bruniquel D, Schwartz RH. Selective, stable demethylation of the interleukin-2 gene enhances transcription by an active process. Nat Immunol. 2003;4(3):235–240.
  • Oswald J, Engemann S, Lane N, et al. Active demethylation of the paternal genome in the mouse zygote. Curr Biol. 2000;10(8):475–478.
  • Zhang F, Pomerantz JH, Sen G, Palermo AT, Blau HM. Active tissue-specific DNA demethylation conferred by somatic cell nuclei in stable heterokaryons. Proc Natl Acad Sci U S A. 2007;104(11):4395–4400.
  • Martinowich K, Hattori D, Wu H, et al. DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation. Science. 2003;302(5646):890–893.
  • Tahiliani M, Koh KP, Shen Y, et al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science. 2009;324(5929):930–935.
  • Ito S, D’Alessio AC, Taranova OV Hong K, Sowers LC, Zhang Y. Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature. 2010;466(7310):1129–1133.
  • Wu H, Zhang Y. Mechanisms and functions of Tet protein-mediated 5-methylcytosine oxidation. Genes Dev. 2011;25(23):2436–2452.
  • Ito S, Shen L, Dai Q, et al. Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science. 2011;333(6047):1300–1303.
  • Bhutani N, Burns DM, Blau HM. DNA demethylation dynamics. Cell. 2011;146(6):866–872.
  • Jeffery L, Nakielny S. Components of the DNA methylation system of chromatin control are RNA-binding proteins. J Biol Chem. 2004;279(47):49479–49487.
  • Hendrich B, Bird A. Identification and characterization of a family of mammalian methyl-CpG binding proteins. Mol Cell Biol. 1998;18(11):6538–6547.
  • Zhang Y, Ng HH, Erdjument-Bromage H, Tempst P, Bird A, Reinberg D. Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation. Genes Dev. 1999;13(15):1924–1935.
  • Yildirim O, Li R, Hung JH, et al. Mbd3/NURD complex regulates expression of 5-hydroxymethylcytosine marked genes in embryonic stem cells. Cell. 2011;147(7):1498–1510.
  • Wang GG, Allis CD, Chi P. Chromatin remodeling and cancer, Part I: Covalent histone modifications. Trends Mol Med. 2007;13(9):363–372.
  • Tan M, Luo H, Lee S, et al. Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification. Cell. 2011;146(6):1016–1028.
  • Kouzarides T. Chromatin modifications and their function. Cell. 2007;128(4):693–705.
  • Shogren-Knaak M, Peterson CL. Switching on chromatin: mechanistic role of histone H4-K16 acetylation. Cell Cycle. 2006;5(13):1361–1365.
  • Shogren-Knaak M, Ishii H, Sun JM, Pazin MJ, Davie JR, Peterson CL. Histone H4-K16 acetylation controls chromatin structure and protein interactions. Science. 2006;311(5762):844–847.
  • Strahl BD, Allis CD. The language of covalent histone modifications. Nature. 2000;403(6765):41–45.
  • Rando OJ. Combinatorial complexity in chromatin structure and function: revisiting the histone code. Curr Opin Genet Dev. 2012;22(2):148–155.
  • Zain J, O’Connor OA. Targeting histone deacetylases in the treatment of B- and T-cell malignancies. Invest New Drugs. 2010;28 Suppl 1: S58–S78.
  • Kim HJ, Bae SC. Histone deacetylase inhibitors: molecular mechanisms of action and clinical trials as anti-cancer drugs. Am JTransl Res. 2011;3(2):166–179.
  • Dietz KC, Casaccia P. HDAC inhibitors and neurodegeneration: at the edge between protection and damage. Pharmacol Res. 2010;62(1):11–17.
  • Grabiec AM, Tak PP, Reedquist KA. Function of histone deacetylase inhibitors in inflammation. Crit Rev Immunol. 2011;31(3):233–263.
  • Barski A, Cuddapah S, Cui K, et al. High-resolution profiling of histone methylations in the human genome. Cell. 2007;129(4):823–837.
  • Heintzman ND, Stuart RK, Hon G, et al. Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nat Genet. 2007;39(3):311–318.
  • Schones DE, Cui K, Cuddapah S, et al. Dynamic regulation of nucleosome positioning in the human genome. Cell. 2008;132(5):887–898.
  • Fish JE, Yan MS, Matouk CC, et al. Hypoxic repression of endothelial nitric-oxide synthase transcription is coupled with eviction of promoter histones. J Biol Chem. 2010;285(2):810–826.
  • Flaus A, Owen-Hughes T. Mechanisms for ATP-dependent chromatin remodelling: the means to the end. FEBS J. 2011;278(19):3579–3595.
  • Creyghton MP, Markoulaki S, Levine SS, et al. H2AZ is enriched at polycomb complex target genes in ES cells and is necessary for lineage commitment. Cell. 2008;135(4):649–661.
  • Bai L, Morozov AV Gene regulation by nucleosome positioning. Trends Genet. 2010;26(11):476–483.
  • Rinn JL, Chang HY. Genome regulation by long noncoding RNAs. Annu Rev Biochem. 2012;81:145–166.
  • Tryndyak VP, Beland FA, Pogribny IP. E-cadherin transcriptional down-regulation by epigenetic and microRNA-200 family alterations is related to mesenchymal and drug-resistant phenotypes in human breast cancer cells. Int J Cancer. 2010;126(11):2575–2583.
  • Kim DH, Saetrom P, Snove O Jr, Rossi JJ. MicroRNA-directed transcriptional gene silencing in mammalian cells. Proc Natl Acad Sci USA. 2008;105(42):16230–16235.
  • Rink C, Khanna S. MicroRNA in ischemic stroke etiology and pathology. Physiol Genomics. 2011;43(10):521–528.
  • Ho JJ, Metcalf JL, Yan MS, et al. Functional importance of dicer protein in the adaptive cellular response to hypoxia. J Biol Chem. 2012;287(34):29003–29020.
  • Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet. 2009;10(3):155–159.
  • Erwin JA, Lee JT. New twists in X-chromosome inactivation. Current Opin Cell Biol. 2008;20(3):349–355.
  • Mikkelsen TS, Ku M, Jaffe DB, et al. Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature. 2007;448(7153):553–560.
  • Guttman M, Amit I, Garber M, et al. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature. 2009;458(7235):223–227.
  • Khalil AM, Guttman M, Huarte M, et al. Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci U S A. 2009;106(28):11667–11672.
  • Wang KC, Yang YW, Liu B, et al. A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression. Nature. 2011;472(7341):120–124.
  • Rinn JL, Kertesz M, Wang JK, et al. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell. 2007;129(7):1311–1323.
  • Kotake Y, Nakagawa T, Kitagawa K, et al. Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15(INK4B) tumor suppressor gene. Oncogene. 2011;30(16):1956–1962.
  • Manolio TA. Genomewide association studies and assessment of the risk of disease. N Engl J Med. 2010;363(2):166–176.
  • Fraga MF, Ballestar E, Paz MF, et al. Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci U S A. 2005;102(30):10604–10609.
  • Yang X, Smith SL, Tian XC, Lewin HA, Renard JP, Wakayama T. Nuclear reprogramming of cloned embryos and its implications for therapeutic cloning. Nat Genet. 2007;39(3):295–302.
  • Morgan HD, Sutherland HG, Martin DI, Whitelaw E. Epigenetic inheritance at the agouti locus in the mouse. Nat Genet. 1999;23(3):314–318.
  • Chan TL, Yuen ST, Kong CK, et al. Heritable germline epimutation of MSH2 in a family with hereditary nonpolyposis colorectal cancer. Nat Genet. 2006;38(10):1178–1183.
  • Hitchins MP, Wong JJ, Suthers G, et al. Inheritance of a cancer-associated MLH1 germ-line epimutation. N Engl J Med. 2007;356(7):697–705.
  • Suter CM, Martin DI, Ward RL. Germline epimutation of MLH1 in individuals with multiple cancers. Nat Genet. 2004;36(5):497–501.
  • Freson K, Izzi B, Van Geet C. From genetics to epigenetics in platelet research. Thromb Res. 2012;129(3):325–329.
  • Goodeve AC, Perry DJ, Cumming T, et al. Genetics of haemostasis. Haemophilia. 2012;18 Suppl 4:73–80.
  • Guttman M, Rinn JL. Modular regulatory principles of large noncoding RNAs. Nature. 2012;482(7385):339–346.
  • Wilcox JN, Subramanian RR, Sundell CL, et al. Expression of multiple isoforms of nitric oxide synthase in normal and atherosclerotic vessels. Arterioscler Thromb Vasc Biol. 1997;17(11):2479–2488.
  • Oemar BS, Tschudi MR, Godoy N, Brovkovich V Malinski T, Luscher TF. Reduced endothelial nitric oxide synthase expression and production in human atherosclerosis. Circulation. 1998;97(25):2494–2498.
  • Brown MS, Goldstein JL. A receptor-mediated pathway for cholesterol homeostasis. Science. 1986;232(4746):34–47.
  • Malek AM, Alper SL, Izumo S. Hemodynamic shear stress and its role in atherosclerosis. JAMA. 1999;282(21):2035–2042.
  • Won D, Zhu SN, Chen M, et al. Relative reduction of endothelial nitric-oxide synthase expression and transcription in atherosclerosis-prone regions of the mouse aorta and in an in vitro model of disturbed flow. Am J Pathol. 2007;171(5):1691–1704.
  • Hajra L, Evans AI, Chen M, Hyduk SJ, Collins T, Cybulsky MI. The NF-kappa B signal transduction pathway in aortic endothelial cells is primed for activation in regions predisposed to atherosclerotic lesion formation. Proc Natl Acad Sci U S A. 2000;97(16):9052–9057.
  • Cui X, Chopp M, Zacharek A, Zhang C, Roberts C, Chen J. Role of endothelial nitric oxide synthetase in arteriogenesis after stroke in mice. Neuroscience. 2009;159(2):744–750.
  • Lo EH, Hara H, Rogowska J, et al. Temporal correlation mapping analysis of the hemodynamic penumbra in mutant mice deficient in endothelial nitric oxide synthase gene expression. Stroke. 1996;27(8):1381–1385.
  • Huang Z, Huang PL, Panahian N, Dalkara T, Fishman MC, Moskowitz MA. Effects of cerebral ischemia in mice deficient in neuronal nitric oxide synthase. Science. 1994;265(5180):1883–1885.
  • Tsui AK, Marsden PA, Mazer CD, et al. Priming of hypoxia-inducible factor by neuronal nitric oxide synthase is essential for adaptive responses to severe anemia. Proc Natl Acad Sci U S A. 2011;108(42):17544–17549.
  • Pruss H, Prass K, Ghaeni L, et al. Inducible nitric oxide synthase does not mediate brain damage after transient focal cerebral ischemia in mice. J Cereb Blood Flow Metab. 2008;28(3):526–539.
  • Fajas L, Fruchart JC, Auwerx J. Transcriptional control of adipogenesis. Curr Opin Cell Biol. 1998;10(2):165–173.
  • McKinsey TA, Zhang CL, Olson EN. Signaling chromatin to make muscle. Curr Opin Cell Biol. 2002;14(6):763–772.
  • Marsden PA, Schappert KT, Chen HS, et al. Molecular cloning and characterization of human endothelial nitric oxide synthase. FEBS Lett. 1992;307(3):287–293.
  • Marsden PA, Heng HH, Scherer SW, et al. Structure and chromosomal localization of the human constitutive endothelial nitric oxide synthase gene. J Biol Chem. 1993;268(23):17478–17488.
  • Tai SC, Robb GB, Marsden PA. Endothelial nitric oxide synthase: a new paradigm for gene regulation in the injured blood vessel. Arterioscler Thromb Vasc Biol. 2004;24(3):405–412.
  • Karantzoulis-Fegaras F, Antoniou H, Lai SL, et al. Characterization of the human endothelial nitric-oxide synthase promoter. J Biol Chem. 1999;274(5):3076–3093.
  • Chan Y, Fish JE, D’Abreo C, et al. The cell-specific expression of endothelial nitric-oxide synthase: a role for DNA methylation. J Biol Chem. 2004;279(33):35087–35100.
  • Guillot PV Liu L, Kuivenhoven JA, Guan J, Rosenberg RD, Aird WC. Targeting of human eNOS promoter to the Hprt locus of mice leads to tissue-restricted transgene expression. Physiol Genomics. 2000;2(2):77–83.
  • Teichert AM, Miller TL, Tai SC, et al. In vivo expression profile of an endothelial nitric oxide synthase promoter-reporter transgene. Am J Physiol Heart Circ Physiol. 2000;278(4):H1352–H1361.
  • Fish JE, Matouk CC, Rachlis A, et al. The expression of endothelial nitric-oxide synthase is controlled by a cell-specific histone code. J Biol Chem. 2005;280(26):24824–24838.
  • Fish JE, Matouk CC, Yeboah E, et al. Hypoxia-inducible expression of a natural cis-antisense transcript inhibits endothelial nitric-oxide synthase. J Biol Chem. 2007;282(21):15652–15666.
  • Robb GB, Carson AR, Tai SC, et al. Post-transcriptional regulation of endothelial nitric-oxide synthase by an overlapping antisense mRNA transcript. J Biol Chem. 2004;279(36):37982–37996.
  • Pasmant E, Laurendeau I, Heron D, Vidaud M, Vidaud D, Bieche I. Characterization of a germ-line deletion, including the entire INK4/ ARE locus, in a melanoma-neural system tumor family: identification of ANRIL, an antisense noncoding RNA whose expression coclusters with ARE. Cancer Res. 2007;67(8):3963–3969.
  • Helgadottir A, Thorleifsson G, Manolescu A, et al. A common variant on chromosome 9p21 affects the risk of myocardial infarction. Science. 2007;316(5830):1491–1493.
  • McPherson R, Pertsemlidis A, Kavaslar N, et al. A common allele on chromosome 9 associated with coronary heart disease. Science. 2007;316(5830):1488–1491.
  • Samani NJ, Erdmann J, Hall AS, et al. Genomewide association analysis of coronary artery disease. N Engl J Med. 2007;357(5):443–453.
  • Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 2007;447(7145):661–678.
  • Bilguvar K, Yasuno K, Niemela M, et al. Susceptibility loci for intracranial aneurysm in European and Japanese populations. Nat Genet. 2008;40(12):1472–1477.
  • Burd CE, Jeck WR, Liu Y, Sanoff HK, Wang Z, Sharpless NE. Expression of linear and novel circular forms of an INK4/ARE-associated non-coding RNA correlates with atherosclerosis risk. PLoS Genet. 2010;6(12):e1001233.
  • Congrains A, Kamide K, Katsuya T, et al. CVD-associated non-coding RNA, ANRIL, modulates expression of atherogenic pathways in VSMC. Biochem Biophys Res Commun. 2012;419(4):612–616.
  • Eolkersen L, Kyriakou T, Goel A, et al. Relationship between CAD risk genotype in the chromosome 9p21 locus and gene expression. Identification of eight new ANRIL splice variants. PloS One. 2009;4(11):e7677.
  • Langley B, Brochier C, Rivieccio MA. Targeting histone deacetylases as a multifaceted approach to treat the diverse outcomes of stroke. Stroke. 2009;40(8):2899–2905.
  • Qureshi I, Mehler M. Chromatin-modifying agents for epigenetic reprogramming and endogenous neural stem cell-mediated repair in stroke. Transl Stroke Res. 2011;2(1):7–16.
  • Gil J, Peters G. Regulation of the INK4b-ARE-INK4a tumour suppressor locus: all for one or one for all. Nat Rev Mol Cell Biol. 2006;7(9):667–677.
  • Endres M, Meisel A, Biniszkiewicz D, et al. DNA methyltransferase contributes to delayed ischemic brain injury. J Neurosc. 2000;20(9):3175–3181.
  • Endres M, Ean G, Meisel A, Dirnagl U, Jaenisch R. Effects of cerebral ischemia in mice lacking DNA methyltransferase 1 in post-mitotic neurons. Neuroreport. 2001;12(17):3763–3766.
  • Earaco G, Pancani T, Eormentini L, et al. Pharmacological inhibition of histone deacetylases by suberoylanilide hydroxamic acid specifically alters gene expression and reduces ischemic injury in the mouse brain. Mol Pharmacol. 2006;70(6):1876–1884.
  • Ren M, Leng Y, Jeong M, Leeds PR, Chuang DM. Valproic acid reduces brain damage induced by transient focal cerebral ischemia in rats: potential roles of histone deacetylase inhibition and heat shock protein induction. J Neurochem. 2004;89(6):1358–1367.
  • Yildirim E, Gertz K, Kronenberg G, et al. Inhibition of histone deacetylation protects wildtype but not gelsolin-deficient mice from ischemic brain injury. Exp Neurol. 2008;210(2):531–542.
  • Langley B, D’Annibale MA, Suh K, et al. Pulse inhibition of his-tone deacetylases induces complete resistance to oxidative death in cortical neurons without toxicity and reveals a role for cytoplasmic p21(waf1/cip1) in cell cycle-independent neuroprotection. J Neurosci. 2008;28(1):163–176.
  • Jeyaseelan K, Lim KY, Armugam A. MicroRNA expression in the blood and brain of rats subjected to transient focal ischemia by middle cerebral artery occlusion. Stroke. 2008;39(3):959–966.
  • Dharap A, Bowen K, Place R, Li LC, Vemuganti R. Transient focal ischemia induces extensive temporal changes in rat cerebral microRNAome. J Cereb Blood Flow Metab. 2009;29(4):675–687.
  • Qureshi IA, Mehler MF. Emerging role of epigenetics in stroke: part 1 : DNA methylation and chromatin modifications. Arch Neurol. 2010;67(11):1316–1322.
  • Qureshi IA, Mehler MF. The emerging role of epigenetics in stroke: II. RNA regulatory circuitry. Arch Neurol. 2010;67(12):1435–1441.
  • Qureshi IA, Mehler MF. The emerging role of epigenetics in stroke: III. Neural stem cell biology and regenerative medicine. Arch Neurol. 2011;68(3):294–302.
  • Zaina S, Dossing KB, Lindholm MW, Lund G. Chromatin modification by lipids and lipoprotein components: an initiating event in atherogenesis? Curr Opin Lipidol. 2005;16(5):549–553.