8,287
Views
1
CrossRef citations to date
0
Altmetric
Perspective

Epigenetics Studies of Fetal Alcohol Spectrum Disorder: Where are We Now?

, &
Pages 291-311 | Received 22 Nov 2016, Accepted 19 Dec 2016, Published online: 17 Feb 2017

References

  • Godfrey K , RobinsonS . Maternal nutrition, placental growth and fetal programming . Proc. Nutr. Soc.57 ( 1 ), 105 – 111 ( 1998 ).
  • Hanson MA , GluckmanPD . Developmental origins of health and disease: new insights . Basic Clin. Pharmacol. Toxicol.102 ( 2 ), 90 – 93 ( 2008 ).
  • Meaney MJ . Epigenetics and the biological definition of gene X environment interactions . Child Dev.81 ( 1 ), 41 – 79 ( 2010 ).
  • Boyce WT , KoborMS . Development and the epigenome: the “synapse” of gene-environment interplay . Dev. Sci.18 ( 1 ), 1 – 23 ( 2015 ).
  • Hoyme HE , KalbergWO , ElliottAJet al. Updated clinical guidelines for diagnosing fetal alcohol spectrum disorders . Pediatrics138 ( 2 ), doi:10.1542/peds.2015–4256 ( 2016 ).
  • Stratton K , HoweC , BattagliaF . Fetal Alcohol Syndrome: Diagnosis, Epidemiology, Prevention and Treatment . National Academy Press , Washington, DC .
  • Jones KL , SmithDW . Recognition of the fetal alcohol syndrome in early infancy . Lancet302 ( 7836 ), 999 – 1001 ( 1973 ).
  • Pollard I . Neuropharmacology of drugs and alcohol in mother and fetus . Semin. Fetal Neonatal Med.12 ( 2 ), 106 – 113 ( 2007 ).
  • Carter RC , JacobsonJL , MoltenoCDet al. Fetal alcohol growth restriction and cognitive impairment . Pediatrics138 ( 2 ), 176192 ( 2016 ).
  • Lynch ME , KableJA , ColesCD . Prenatal alcohol exposure, adaptive function, and entry into adult roles in a prospective study of young adults . Neurotoxicol. Teratol.51 , 52 – 60 ( 2015 ).
  • Panczakiewicz AL , GlassL , ColesCDet al. Neurobehavioral deficits consistent across age and sex in youth with prenatal alcohol Exposure . Alcohol. Clin. Exp. Res.40 ( 9 ), 1971 – 1981 ( 2016 ).
  • Doyle LR , MattsonSN . Neurobehavioral disorder associated with prenatal alcohol exposure (ND-PAE): review of evidence and guidelines for assessment . Curr. Dev. Disord. Rep.2 ( 3 ), 175 – 186 ( 2015 ).
  • Astley SJ , OlsonHC , KernsKet al. Neuropyschological and behavioral outcomes from a comprehensive magnetic resonance study of children with fetal alcohol spectrum disorders . Can. J. Clin. Pharmacol.16 ( 1 ), e178 – e201 ( 2009 ).
  • Streissguth AP , O’MalleyK . Neuropsychiatric implications and long-term consequences of fetal alcohol spectrum disorders . Semin. Clin. Neuropsychiatry5 ( 3 ), 177 – 190 ( 2000 ).
  • Moore EM , RileyEP . What happens when children with fetal alcohol spectrum disorders become adults?Curr. Dev. Disord. Rep.2 ( 3 ), 219 – 227 ( 2015 ).
  • Jones KL , SmithDW , UllelandCN , StreissguthP . Pattern of malformation in offspring of chronic alcoholic mothers . Lancet1 ( 7815 ), 1267 – 1271 ( 1973 ).
  • Liu Y , BalaramanY , WangG , NephewKP , ZhouFC . Alcohol exposure alters DNA methylation profiles in mouse embryos at early neurulation . Epigenetics4 ( 7 ), 500 – 511 ( 2009 ).
  • Zhou FC , ZhaoQ , LiuYet al. Alteration of gene expression by alcohol exposure at early neurulation . BMC Genomics12 , 124 ( 2011 ).
  • Hicks SD , MiddletonFA , MillerMW . Ethanol-induced methylation of cell cycle genes in neural stem cells . J. Neurochem.114 ( 6 ), 1767 – 1780 ( 2010 ).
  • Veazey KJ , CarnahanMN , MullerD , MirandaRC , GoldingMC . Alcohol-induced epigenetic alterations to developmentally crucial genes regulating neural stemness and differentiation . Alcohol. Clin. Exp. Res.37 ( 7 ), 1111 – 1122 ( 2013 ).
  • Veazey KJ , ParnellSE , MirandaRC , GoldingMC . Dose-dependent alcohol-induced alterations in chromatin structure persist beyond the window of exposure and correlate with fetal alcohol syndrome birth defects . Epigenetics Chromatin.8 ( 1 ), 39 ( 2015 ).
  • Balaraman S , Winzer-SerhanUH , MirandaRC . Opposing actions of ethanol and nicotine on microRNAs are mediated by nicotinic acetylcholine receptors in fetal cerebral cortical-derived neural progenitor cells . Alcohol. Clin. Exp. Res.36 ( 10 ), 1669 – 1677 ( 2012 ).
  • Swanson JM , EntringerS , BussC , WadhwaPD . Developmental origins of health and disease: environmental exposures . Semin. Reprod. Med.27 ( 5 ), 391 – 402 ( 2009 ).
  • Hellemans KGC , SliwowskaJH , VermaP , WeinbergJ . Prenatal alcohol exposure: fetal programming and later life vulnerability to stress, depression and anxiety disorders . Neurosci. Biobehav. Rev.34 ( 6 ), 791 – 807 ( 2010 ).
  • Yuen RKC , NeumannSMA , FokAKet al. Extensive epigenetic reprogramming in human somatic tissues between fetus and adult . Epigenetics Chromatin.4 , 7 ( 2011 ).
  • Shulha HP , CheungI , GuoY , AkbarianS , WengZ . Coordinated cell type-specific epigenetic remodeling in prefrontal cortex begins before birth and continues into early adulthood . PLoS Genet.9 ( 4 ), e1003433 ( 2013 ).
  • Kobor MS , WeinbergJ . Focus on: epigenetics and fetal alcohol spectrum disorders . Alcohol Res. Health34 ( 1 ), 29 – 37 ( 2011 ).
  • Bird A . Perceptions of epigenetics . Nature447 ( 7143 ), 396 – 398 ( 2007 ).
  • Ziller MJ , GuH , MüllerFet al. Charting a dynamic DNA methylation landscape of the human genome . Nature500 ( 7463 ), 477 – 81 ( 2013 ).
  • Kleiber ML , LauferBI , StringerRL , SinghSM . Third trimester-equivalent ethanol exposure is characterized by an acute cellular stress response and an ontogenetic disruption of genes critical for synaptic establishment and function in mice . Dev. Neurosci.36 ( 6 ), 499 – 519 ( 2014 ).
  • Kleiber ML , LauferBI , WrightE , DiehlEJ , SinghSM . Long-term alterations to the brain transcriptome in a maternal voluntary consumption model of fetal alcohol spectrum disorders . Brain Res.1458 , 18 – 33 ( 2012 ).
  • Kleiber ML , ManthaK , StringerRL , SinghSM . Neurodevelopmental alcohol exposure elicits long-term changes to gene expression that alter distinct molecular pathways dependent on timing of exposure . J. Neurodev. Disord.5 ( 1 ), 6 ( 2013 ).
  • Downing C , FlinkS , Florez-McClureML , JohnsonTE , TabakoffB , KechrisKJ . Gene expression changes in C57BL/6J and DBA/2J mice following prenatal alcohol exposure . Alcohol. Clin. Exp. Res.36 ( 9 ), 1519 – 1529 ( 2012 ).
  • Lussier AA , StepienKA , NeumannSM , PavlidisP , KoborMS , WeinbergJ . Prenatal alcohol exposure alters steady-state and activated gene expression in the adult rat brain . Alcohol. Clin. Exp. Res.39 ( 2 ), 251 – 261 ( 2015 ).
  • Green ML , SinghAV , ZhangY , NemethKA , SulikKK , KnudsenTB . Reprogramming of genetic networks during initiation of the fetal alcohol syndrome . Dev. Dyn.236 ( 2 ), 613 – 631 ( 2007 ).
  • Hard ML , AbdolellM , RobinsonBH , KorenG . Gene-expression analysis after alcohol exposure in the developing mouse . J. Lab. Clin. Med.145 ( 1 ), 47 – 54 ( 2005 ).
  • Jones PA , TakaiD . The role of DNA methylation in mammalian epigenetics . Science293 ( 5532 ), 1068 – 1070 ( 2001 ).
  • Jones PA . Functions of DNA methylation: islands, start sites, gene bodies and beyond . Nat. Rev. Genet.13 ( 7 ), 484 – 492 ( 2012 ).
  • Lister R , MukamelEA , NeryJRet al. Global epigenomic reconfiguration during mammalian brain development . Science341 ( 6146 ), 1237905 ( 2013 ).
  • Guo JU , SuY , ShinJHet al. Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain . Nat. Neurosci.17 ( 2 ), 215 – 222 ( 2014 ).
  • Tate PH , BirdAP . Effects of DNA methylation on DNA-binding proteins and gene expression . Curr. Opin. Genet. Dev.3 ( 2 ), 226 – 231 ( 1993 ).
  • Shukla S , KavakE , GregoryMet al. CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing . Nature479 ( 7371 ), 74 – 79 ( 2011 ).
  • Maunakea AK , ChepelevI , CuiK , ZhaoK . Intragenic DNA methylation modulates alternative splicing by recruiting MeCP2 to promote exon recognition . Cell Res.23 ( 11 ), 1256 – 1269 ( 2013 ).
  • Maunakea AK , NagarajanRP , BilenkyMet al. Conserved role of intragenic DNA methylation in regulating alternative promoters . Nature466 ( 7303 ), 253 – 257 ( 2010 ).
  • Lam LL , EmberlyE , FraserHBet al. Factors underlying variable DNA methylation in a human community cohort . Proc. Natl Acad. Sci. USA109 ( Suppl. 2 ), 17253 – 17260 ( 2012 ).
  • Gutierrez-Arcelus M , LappalainenT , MontgomerySBet al. Passive and active DNA methylation and the interplay with genetic variation in gene regulation . Elife2 ( 2 ), e00523 ( 2013 ).
  • Jones MJ , FejesAP , KoborMS . DNA methylation, genotype and gene expression: who is driving and who is along for the ride?Genome Biol.14 ( 7 ), 126 ( 2013 ).
  • Sadakierska-Chudy A , KostrzewaRM , FilipM . A comprehensive view of the epigenetic landscape part I: DNA methylation, passive and active DNA demethylation pathways and histone variants . Neurotox. Res.27 ( 1 ), 84 – 97 ( 2014 ).
  • Ito S , D’AlessioAC , TaranovaOV , HongK , SowersLC , ZhangY . Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification . Nature466 ( 7310 ), 1129 – 1133 ( 2010 ).
  • Kriaucionis S , HeintzN . The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain . Science ( 80 ), 324 ( 5929 ), 929 – 930 ( 2009 ).
  • Santiago M , AntunesC , GuedesM , SousaN , MarquesCJ . TET enzymes and DNA hydroxymethylation in neural development and function – how critical are they?Genomics104 ( 5 ), 334 – 340 ( 2014 ).
  • Alaghband Y , BredyTW , WoodMA . The role of active DNA demethylation and Tet enzyme function in memory formation and cocaine action . Neurosci. Lett.625 , 40 – 46 ( 2016 ).
  • Wang T , PanQ , LinLet al. Genome-wide DNA hydroxymethylation changes are associated with neurodevelopmental genes in the developing human cerebellum . Hum. Mol. Genet.21 ( 26 ), 5500 – 5510 ( 2012 ).
  • Bock C . Epigenetic biomarker development . Epigenomics1 ( 1 ), 99 – 110 ( 2009 ).
  • Garro AJ , McBethDL , LimaV , LieberCS . Ethanol consumption inhibits fetal DNA methylation in mice: implications for the fetal alcohol syndrome . Alcohol. Clin. Exp. Res.15 ( 3 ), 395 – 398 ( 1991 ).
  • Otero NKH , ThomasJD , SaskiCA , XiaX , KellySJ . Choline supplementation and DNA methylation in the hippocampus and prefrontal cortex of rats exposed to alcohol during development . Alcohol. Clin. Exp. Res.36 ( 10 ), 1701 – 1709 ( 2012 ).
  • Perkins A , LehmannC , LawrenceRC , KellySJ . Alcohol exposure during development: Impact on the epigenome . Int. J. Dev. Neurosci.31 ( 6 ), 391 – 397 ( 2013 ).
  • Chen Y , OzturkNC , ZhouFC . DNA methylation program in developing hippocampus and its alteration by alcohol . PLoS ONE8 ( 3 ), 1 – 11 ( 2013 ).
  • Mukhopadhyay P , RezzougF , KaikausJ , GreeneRM , PisanoMM . Alcohol modulates expression of DNA methyltranferases and methyl CpG-/CpG domain-binding proteins in murine embryonic fibroblasts . Reprod. Toxicol.37 , 40 – 48 ( 2013 ).
  • Nagre NN , SubbannaS , ShivakumarM , PsychoyosD , BasavarajappaBS . CB1-receptor knockout neonatal mice are protected against ethanol-induced impairments of DNMT1, DNMT3A, and DNA methylation . J. Neurochem.132 ( 4 ), 429 – 442 ( 2015 ).
  • Liyanage VRB , ZachariahRM , DavieJR , RastegarM . Ethanol deregulates Mecp2/MeCP2 in differentiating neural stem cells via interplay between 5-methylcytosine and 5-hydroxymethylcytosine at the Mecp2 regulatory elements . Exp. Neurol.265 , 102 – 117 ( 2015 ).
  • Thomas JD , BianeJS , O’BryanKA , O’NeillTM , DominguezHD . Choline supplementation following third-trimester-equivalent alcohol exposure attenuates behavioral alterations in rats . Behav. Neurosci.121 ( 1 ), 120 – 130 ( 2007 ).
  • Wolff GL , KodellRL , MooreSR , CooneyCA . Maternal epigenetics and methyl supplements affect agouti gene expression in Avy/a mice . FASEB J.12 ( 11 ), 949 – 957 ( 1998 ).
  • Kaminen-Ahola N , AholaA , MagaMet al. Maternal ethanol consumption alters the epigenotype and the phenotype of offspring in a mouse model . PLoS Genet.6 ( 1 ), e1000811 ( 2010 ).
  • Vallés S , PitarchJ , Renau-PiquerasJ , GuerriC . Ethanol exposure affects glial fibrillary acidic protein gene expression and transcription during rat brain development . J. Neurochem.69 , 2484 – 2493 ( 1997 ).
  • Maier SE , CramerJA , WestJR , SohrabjiF . Alcohol exposure during the first two trimesters equivalent alters granule cell number and neurotrophin expression in the developing rat olfactory bulb . J. Neurobiol.41 ( 3 ), 414 – 423 ( 1999 ).
  • Downing C , JohnsonTE , LarsonCet al. Subtle decreases in DNA methylation and gene expression at the mouse Igf2 locus following prenatal alcohol exposure: effects of a methyl-supplemented diet . Alcoholism45 ( 1 ), 65 – 71 ( 2011 ).
  • Bekdash RA , ZhangC , SarkarDK . Gestational choline supplementation normalized fetal alcohol-induced alterations in histone modifications, DNA methylation, and proopiomelanocortin (POMC) gene expression in??-endorphin-producing POMC neurons of the hypothalamus . Alcohol. Clin. Exp. Res.37 ( 7 ), 1133 – 1142 ( 2013 ).
  • Zhang CR , HoM-F , VegaMCS , BurneTHJ , ChongS . Prenatal ethanol exposure alters adult hippocampal VGLUT2 expression with concomitant changes in promoter DNA methylation, H3K4 trimethylation and miR-467b-5p levels . Epigenetics Chromatin.8 ( 1 ), 40 ( 2015 ).
  • Ngai YF , SulistyoningrumDC , O’NeillR , InnisSM , WeinbergJ , DevlinAM . Prenatal alcohol exposure alters methyl metabolism and programs serotonin transporter and glucocorticoid receptor expression in brain . Am. J. Physiol. Regul. Integr. Comp. Physiol.309 ( 5 ), R613 – R622 ( 2015 ).
  • Marjonen H , SierraA , NymanAet al. Early maternal alcohol consumption alters hippocampal DNA methylation, gene expression and volume in a mouse model . PLoS ONE10 ( 5 ), e0124931 ( 2015 ).
  • Zhou FC , ChenY , LoveA . Cellular DNA methylation program during neurulation and its alteration by alcohol exposure . Birth Defects Res. Part A - Clin. Mol. Teratol.91 ( 8 ), 703 – 715 ( 2011 ).
  • Laufer BI , ManthaK , KleiberML , DiehlEJ , AddisonSMF , SinghSM . Long-lasting alterations to DNA methylation and ncRNAs could underlie the effects of fetal alcohol exposure in mice . Dis. Model. Mech.6 ( 4 ), 977 – 92 ( 2013 ).
  • Krishnamoorthy M , GerweBA , ScharerCDet al. Ethanol alters proliferation and differentiation of normal and chromosomally abnormal human embryonic stem cell-derived neurospheres . Birth Defects Res. Part B Dev. Reprod. Toxicol.98 ( 3 ), 283 – 295 ( 2013 ).
  • Khalid O , KimJJ , KimHSet al. Gene expression signatures affected by alcohol-induced DNA methylomic deregulation in human embryonic stem cells . Stem Cell Res.12 ( 3 ), 791 – 806 ( 2014 ).
  • Chater-Diehl EJ , LauferBI , CastellaniCA , AlberryBL , SinghSM . Alteration of gene expression, DNA methylation, and histone methylation in free radical scavenging networks in adult mouse hippocampus following fetal alcohol exposure . PLoS ONE11 ( 5 ), e0154836 ( 2016 ).
  • Laufer BI , KapalangaJ , CastellaniCA , DiehlEJ , YanL , SinghSM . Associative DNA methylation changes in children with prenatal alcohol exposure . Epigenomics7 ( 8 ), 1259 – 1274 ( 2015 ).
  • Portales-Casamar E , LussierAA , JonesMJet al. DNA methylation signature of human fetal alcohol spectrum disorder . Epigenetics Chromatin.9 ( 25 ), 81 – 101 ( 2016 ).
  • Kornberg RD . Chromatin structure: a repeating unit of histones and DNA . Science184 ( 4139 ), 868 – 871 ( 1974 ).
  • Luger K , MäderAW , RichmondRK , SargentDF . Crystal structure of the nucleosome core particle at 2.8 Å resolution . Nature389 ( 6648 ), 251 – 260 ( 1997 ).
  • Venkatesh S , SmolleM , LiHet al. Set2 methylation of histone H3 lysine 36 suppresses histone exchange on transcribed genes . Nature489 ( 7416 ), 452 – 455 ( 2013 ).
  • Kouzarides T . Chromatin modifications and their function . Cell128 ( 4 ), 693 – 705 ( 2007 ).
  • Bannister AJ , KouzaridesT . Regulation of chromatin by histone modifications . Cell Res.21 ( 3 ), 381 – 395 ( 2011 ).
  • Bowman GD , PoirierMG . Post-translational modifications of histones that influence nucleosome dynamics . Chem. Rev.115 ( 6 ), 2274 – 2295 ( 2015 ).
  • Du Q , LuuP-L , StirzakerC , ClarkSJ . Methyl-CpG-binding domain proteins: readers of the epigenome . Epigenomics7 ( 6 ), 1051 – 1073 ( 2015 ).
  • Bogdanović O , VeenstraGJC . DNA methylation and methyl-CpG binding proteins: developmental requirements and function . Chromosoma118 ( 5 ), 549 – 565 ( 2009 ).
  • Amir RE , Van den VeyverIB , WanM , TranCQ , FranckeU , ZoghbiHY . Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2 . Nat. Genet.23 , 185 – 188 ( 1999 ).
  • Ramadoss J , LiaoWX , ChenDB , MagnessRR . High-throughput caveolar proteomic signature profile for maternal binge alcohol consumption . Alcoholism44 ( 7–8 ), 691 – 697 ( 2010 ).
  • Guo W , CrosseyEL , ZhangLet al. Alcohol exposure decreases CREB binding protein expression and histone acetylation in the developing cerebellum . PLoS ONE6 ( 5 ) ( 2011 ).
  • Zhong L , ZhuJ , LvTet al. Ethanol and its metabolites induce histone lysine 9 acetylation and an alteration of the expression of heart development-related genes in cardiac progenitor cells . Cardiovasc. Toxicol.10 ( 4 ), 268 – 274 ( 2010 ).
  • Govorko D , BekdashRA , ZhangC , SarkarDK . Male germline transmits fetal alcohol adverse effect on hypothalamic proopiomelanocortin gene across generations . Biol. Psychiatry72 ( 5 ), 378 – 388 ( 2012 ).
  • Subbanna S , ShivakumarM , UmapathyNSet al. G9a-mediated histone methylation regulates ethanol-induced neurodegeneration in the neonatal mouse brain . Neurobiol. Dis.54 , 475 – 485 ( 2013 ).
  • Subbanna S , NagreNN , ShivakumarM , UmapathyNS , PsychoyosD , BasavarajappaBS . Ethanol induced acetylation of histone at G9a exon1 and G9a-mediated histone H3 dimethylation leads to neurodegeneration in neonatal mice . Neuroscience258 , 422 – 432 ( 2014 ).
  • Zhang W , PengC , ZhengMet al. Prenatal alcohol exposure causes the over-expression of DHAND and EHAND by increasing histone H3K14 acetylation in C57 BL/6 mice . Toxicol. Lett.228 ( 3 ), 140 – 146 ( 2014 ).
  • Peng C , ZhuJ , SunHCet al. Inhibition of histone H3K9 acetylation by anacardic acid can correct the over-expression of Gata4 in the hearts of fetal mice exposed to alcohol during pregnancy . PLoS ONE9 ( 8 ), e104135 ( 2014 ).
  • Chung H-Y , ChangC-T , YoungH-W , HuSP , TzouW-S , HuC-H . Ethanol inhibits retinal and CNS differentiation due to failure of cell cycle exit via an apoptosis-independent pathway . Neurotoxicol. Teratol.38 , 92 – 103 ( 2013 ).
  • Goldowitz D , LussierAA , BoyleJKet al. Molecular pathways underpinning ethanol-induced neurodegeneration . Front. Genet.5 , 203 ( 2014 ).
  • Subbanna S , BasavarajappaBS . Pre-administration of G9a/GLP inhibitor during synaptogenesis prevents postnatal ethanol-induced LTP deficits and neurobehavioral abnormalities in adult mice . Exp. Neurol.261 , 34 – 43 ( 2014 ).
  • Subbanna S , NagreNN , UmapathyNS , PaceBS , BasavarajappaBS . Ethanol exposure induces neonatal neurodegeneration by enhancing CB1R Exon1 Histone H4K8 acetylation and up-regulating CB1R function causing neurobehavioral abnormalities in adult mice . Int. J. Neuropsychopharmacol.18 ( 5 ), 1 – 15 ( 2015 ).
  • Kim P , ParkJH , ChoiCSet al. Effects of ethanol exposure during early pregnancy in hyperactive, inattentive and impulsive behaviors and MeCP2 expression in rodent offspring . Neurochem. Res.38 ( 3 ), 620 – 631 ( 2013 ).
  • Dasmahapatra AK , KhanIA . Modulation of DNA methylation machineries in Japanese rice fish (Oryzias latipes) embryogenesis by ethanol and 5-azacytidine . Comp. Biochem. Physiol. Part C Toxicol. Pharmacol.179 , 174 – 183 ( 2016 ).
  • Geisler S , CollerJ . RNA in unexpected places: long non-coding RNA functions in diverse cellular contexts . Nat. Rev. Mol. Cell Biol.14 ( 11 ), 699 – 712 ( 2013 ).
  • Orom UA , DerrienT , BeringerMet al. Long noncoding RNAs with enhancer-like function in human cells . Cell143 ( 1 ), 46 – 58 ( 2010 ).
  • Rinn JL , KerteszM , WangJKet al. Functional demarcation of active and silent chromatin domains in Human HOX loci by noncoding RNAs . Cell129 ( 7 ), 1311 – 1323 ( 2007 ).
  • Wutz A . Gene silencing in X-chromosome inactivation: advances in understanding facultative heterochromatin formation . Nat. Rev. Genet.12 ( 8 ), 542 – 553 ( 2011 ).
  • Wang KC , ChangHY . Molecular mechanisms of long noncoding RNAs . Mol. Cell43 ( 6 ), 904 – 914 ( 2011 ).
  • Kapranov P , St LaurentG , RazTet al. The majority of total nuclear-encoded non-ribosomal RNA in a human cell is “dark matter” un-annotated RNA . BMC Biol.8 , 149 ( 2010 ).
  • Gustincich S , SandelinA , PlessyCet al. The complexity of the mammalian transcriptome . J. Physiol.575 ( 2 ), 321 – 332 ( 2006 ).
  • Spadaro PA , BredyTW . Emerging role of non-coding RNA in neural plasticity, cognitive function, and neuropsychiatric disorders . Front. Genet.3 , 1 – 16 ( 2012 ).
  • Williams JM , BeckTF , PearsonDM , ProudMB , SauWC , ScottDA . A 1q42 deletion involving DISC1, DISC2, and TSNAX in an autism spectrum disorder . Am. J. Med. Genet. Part A149 ( 8 ), 1758 – 1762 ( 2009 ).
  • Ziats MN , RennertOM . Aberrant expression of long noncoding RNAs in autistic brain . J. Mol. Neurosci.49 ( 3 ), 589 – 593 ( 2013 ).
  • Pastori C , PeschanskyVJ , BarbouthD , MehtaA , SilvaJP , WahlestedtC . Comprehensive analysis of the transcriptional landscape of the human FMR1 gene reveals two new long noncoding RNAs differentially expressed in Fragile X syndrome and Fragile X-associated tremor/ataxia syndrome . Hum. Genet.133 ( 1 ), 59 – 67 ( 2014 ).
  • Petazzi P , SandovalJ , SzczesnaKet al. Dysregulation of the long non-coding RNA transcriptome in a Rett syndrome mouse model . RNA Biol.10 ( 7 ), 1197 – 1203 ( 2013 ).
  • Millar JK , Wilson-AnnanJC , AndersonSet al. Disruption of two novel genes by a translocation co-segregating with schizophrenia . Hum. Mol. Genet.9 ( 9 ), 1415 – 1423 ( 2000 ).
  • Barry G , BriggsJ , VanichkinaDet al. The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing . Mol. Psychiatry19 , 486 – 494 ( 2013 ).
  • Spadaro PA , FlavellCR , WidagdoJet al. Long noncoding RNA-directed epigenetic regulation of gene expression is associated with anxiety-like behavior in mice . Biol. Psychiatry78 ( 12 ), 848 – 859 ( 2015 ).
  • Sathyan P , GoldenHB , MirandaRC . Competing interactions between micro-RNAs determine neural progenitor survival and proliferation after ethanol exposure: evidence from an ex vivo model of the fetal cerebral cortical neuroepithelium . J. Neurosci.27 ( 32 ), 8546 – 8557 ( 2007 ).
  • Wang L-L , ZhangZ , LiQet al. Ethanol exposure induces differential microRNA and target gene expression and teratogenic effects which can be suppressed by folic acid supplementation . Hum. Reprod.24 ( 3 ), 562 – 579 ( 2009 ).
  • Soares AR , PereiraPM , FerreiraVet al. Ethanol exposure induces upregulation of specific microRNAs in zebrafish embryos . Toxicol. Sci.127 ( 1 ), 18 – 28 ( 2012 ).
  • Stringer RL , LauferBI , KleiberML , SinghSM . Reduced expression of brain cannabinoid receptor 1 (Cnr1) is coupled with an increased complementary micro-RNA (miR-26b) in a mouse model of fetal alcohol spectrum disorders . Clin. Epigenetics5 ( 1 ), 14 ( 2013 ).
  • Pappalardo-Carter DL , BalaramanS , SathyanP , CarterES , ChenWJA , MirandaRC . Suppression and epigenetic regulation of MiR-9 contributes to ethanol teratology: Evidence from zebrafish and murine fetal neural stem cell models . Alcohol. Clin. Exp. Res.37 ( 10 ), 1657 – 1667 ( 2013 ).
  • Mantha K , LauferBI , SinghSM . Molecular changes during neurodevelopment following second-trimester binge ethanol exposure in a mouse model of fetal alcohol spectrum disorder: From immediate effects to long-term adaptation . Dev. Neurosci.36 ( 1 ), 29 – 43 ( 2014 ).
  • Ignacio C , MooneySM , MiddletonFA . Effects of acute prenatal exposure to ethanol on microRNA expression are ameliorated by social enrichment . Front. Pediatr.2 , 103 ( 2014 ).
  • Balaraman S , LundeER , SawantO , CuddTA , WashburnSE , MirandaRC . Maternal and neonatal plasma microrna biomarkers for fetal alcohol exposure in an ovine model . Alcohol. Clin. Exp. Res.38 ( 5 ), 1390 – 1400 ( 2014 ).
  • Qi Y , ZhangM , LiHet al. MicroRNA-29b regulates ethanol-induced neuronal apoptosis in the developing cerebellum through SP1/RAX/PKR Cascade . J. Biol. Chem.289 ( 14 ), 10201 – 10210 ( 2014 ).
  • Guo Y , ChenY , CarreonS , QiangM . Chronic intermittent ethanol exposure and its removal induce a different miRNA expression pattern in primary cortical neuronal cultures . Alcohol. Clin. Exp. Res.36 ( 6 ), 1058 – 1066 ( 2012 ).
  • Miranda RC . MicroRNAs and ethanol toxicity . Int. Rev. Neurobiol.115 , 245 – 284 ( 2014 ).
  • Tal TL , FranzosaJA , TiltonSCet al. MicroRNAs control neurobehavioral development and function in zebrafish . FASEB J.26 ( 4 ), 1452 – 1461 ( 2012 ).
  • Balaraman S , SchaferJJ , TsengAMet al. Plasma miRNA profiles in pregnant women predict infant outcomes following prenatal alcohol exposure . PLoS ONE11 ( 11 ), e0165081 ( 2016 ).
  • Widagdo J , ZhaoQ , KempenMet al. Experience-dependent accumulation of N 6-methyladenosine in the prefrontal cortex is associated with memory processes in mice . J. Neurosci.36 ( 25 ), 6771 – 6777 ( 2016 ).
  • Clayton JA , CollinsFS . NIH to balance sex in cell and animal studies . Nature509 ( 7500 ), 282 – 283 ( 2014 ).
  • Zhang FF , CardarelliR , CarrollJet al. Significant differences in global genomic DNA methylation by gender and race/ethnicity in peripheral blood . Epigenetics6 ( 5 ), 623 – 629 ( 2011 ).
  • Hellemans KGC , VermaP , YoonE , YuW , WeinbergJ . Prenatal alcohol exposure increases vulnerability to stress and anxiety-like disorders in adulthood . Ann. N. Y. Acad. Sci.1144 , 154 – 175 ( 2008 ).
  • Bale TL , EppersonCN . Sex differences and stress across the lifespan . Nat. Neurosci.18 ( 10 ), 1413 – 1420 ( 2015 ).
  • Oldehinkel AJ , BoumaEMC . Sensitivity to the depressogenic effect of stress and HPA-axis reactivity in adolescence: a review of gender differences . Neurosci. Biobehav. Rev.35 ( 8 ), 1757 – 1770 ( 2011 ).
  • Patten AR , FontaineCJ , ChristieBR . A comparison of the different animal models of fetal alcohol spectrum disorders and their use in studying complex behaviors . Front. Pediatr.2 , 93 ( 2014 ).
  • van Otterdijk SD , MichelsKB . Transgenerational epigenetic inheritance in mammals: how good is the evidence?FASEB J.30 , 1 – 9 ( 2016 ).
  • Gutierrez-Arcelus M , LappalainenT , MontgomerySBet al. Passive and active DNA methylation and the interplay with genetic variation in gene regulation . Elife2 , e00523 – e00523 ( 2013 ).
  • Fraser HB , LamLL , NeumannSM , KoborMS . Population-specificity of human DNA methylation . Genome Biol.13 ( 2 ), R8 ( 2012 ).
  • Heyn H , MoranS , Hernando-HerraezIet al. DNA methylation contributes to natural human variation . Genome Res.23 ( 9 ), 1363 – 1372 ( 2013 ).
  • Moen EL , ZhangX , MuWet al. Genome-wide variation of cytosine modifications between European and African populations and the implications for complex traits . Genetics194 ( 4 ), 987 – 996 ( 2013 ).
  • Jones MJ , GoodmanSJ , KoborMS . DNA methylation and healthy human aging . Aging Cell14 ( 6 ), 924 – 932 ( 2015 ).
  • Kelleher E , CorvinA . Overlapping etiology of neurodevelopmental disorders . In : The Genetics of Neurodevelopmental Disorders . John Wiley & Sons, Inc. , NJ, USA , 29 – 48 ( 2015 ).
  • Jones KL , SmithDW . Recognition of the fetal alcohol syndrome in early infancy . Lancet302 ( 7836 ), 999 – 1001 ( 1973 ).
  • Lemoine P , HarousseauH , BorteyruJ , MenuetJ . Les enfants des parents alcoholiques: anomolies observées a propos de 127 cas . Ouest Med.8 , 476 – 482 ( 1968 ).
  • May PA , GossageJP . Estimating the prevalence of fetal alcohol syndrome: a summary . Alcohol Res. Health25 ( 3 ), 159 – 167 ( 2001 ).
  • May PA , BaeteA , RussoJet al. Prevalence and characteristics of fetal alcohol spectrum disorders . Pediatrics134 ( 5 ), 855 – 866 ( 2014 ).
  • May PA , KeasterC , BozemanRet al. Prevalence and characteristics of fetal alcohol syndrome and partial fetal alcohol syndrome in a Rocky Mountain Region City . Drug Alcohol Depend.155 , 118 – 127 ( 2015 ).
  • Murawski N , MooreE , ThomasJ , RileyE . Advances in diagnosis and treatment of fetal alcohol spectrum disorders from animal models to human studies . Alcohol. Res.37 ( 1 ), 97 – 108 ( 2015 ).