Chromodomain helicase DNA-binding proteins and neurodevelopmental disorders

Abstract

The significance of epigenomic regulation is now established in the etiology of neurodevelopmental disorders (NDDs). Epigenomic regulatory processes include chromatin remodeling as a major regulator of gene expression in development. Chromatin remodeling is an enzymatic process carried out by large multi-unit protein complexes, of which the chromodomain helicase DNA-binding proteins comprise one of four recognized major protein families, named the chromodomain helicase DNA-binding (CHD) family. There are nine CHD proteins (CHD1-9) encoded by nine correspondingly named CHD genes. Remarkably, five of the nine CHDs are already recognized to be causative of autosomal dominant syndromic NDD. In this review, we discuss the contribution of all CHDs to NDDs. And, we specifically focus on molecular studies involving CHD8 of which several have been recently published and scarcely reviewed. The widespread nature of downstream targeting for CHD8, as well as the finding of autosomal dominant disease for the majority of CHDs in general, implicates this family of chromatin remodelers as major players in NDD causation.

Keywords

CHD8 / intellectual disability / neurodevelopmental disorders / autism spectrum disorder / CHDs / chromodomain helicase DNA-binding proteins / epigenomics / epigenetics

References

[1] WaddingtonCH.The epigenotype..Int J Epidemiol1942;41:10-3

[2] FireA,MontgomeryMK,DriverSE.Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans..Nature1998;391:806-11

[3] SmithZD.DNA methylation: roles in mammalian development..Nat Rev Genet2013;14:204-20

[4] WalshCP.Cytosine methylation and DNA repair..Curr Top Microbiol Immunol2006;301:283-315

[5] MedvedevaYA,KulakovskiyIV,BhuyanMSI.Effects of cytosine methylation on transcription factor binding sites..BMC genomics.2014;15:119 PMCID:PMC3986887

[6] PatilV,HessonLB.The evidence for functional non-CpG methylation in mammalian cells..Epigenetics2014;9:823-8 PMCID:PMC4065179

[7] VarleyKE,BowlingKM,ReddyTE.Dynamic DNA methylation across diverse human cell lines and tissues..Genome Res2013;23:555-67 PMCID:PMC3589544

[8] ShayevitchR,KeydarI.The importance of DNA methylation of exons on alternative splicing..RNA.2018;24:1351-62 PMCID:PMC6140467

[9] TrivediM,ZhangY.DNA methylation, hydroxymethylation and formylation in human frontal cortex of autistic and schizophrenic subjects..Faseb J2017;31:468.3

[10] BannisterAJ.Regulation of chromatin by histone modifications..Cell Res2011;21:381-95 PMCID:PMC3193420

[11] BogliottiYS.Mechanisms of histone H3 lysine 27 trimethylation remodeling during early mammalian development..Epigenetics2012;7:976-81 PMCID:PMC3515017

[12] LiuX,LiuW,LiC.Distinct features of H3K4me3 and H3K27me3 chromatin domains in pre-implantation embryos..Nature2016;537:558-62

[13] MillerJL.The role of DNA methylation and histone modifications in transcriptional regulation in humans..Subcell Biochem2013;61:289-317 PMCID:PMC6611551

[14] ClapierCR.The biology of chromatin remodeling complexes..Annu Rev Biochem2009;78:273-304

[15] HyunK,ParkK.Writing, erasing and reading histone lysine methylations..Exp Mol Med2017;49:e324 PMCID:PMC6130214

[16] MicucciJA,MartinDM.Chromodomain helicase DNA-binding proteins in stem cells and human developmental diseases..Stem Cells Dev2015;24:917-26 PMCID:PMC4390162

[17] MargueronR.Chromatin structure and the inheritance of epigenetic information..Nat Rev Genet2010;11:285-96 PMCID:PMC3760772

[18] RudnizkyS,BavlyA,MelamedP.Nucleosome mobility and the regulation of gene expression: insights from single-molecule studies..Protein Sci2017;26:1266-77 PMCID:PMC5477540

[19] Ehrenhofer-MurrayAE.Chromatin dynamics at DNA replication, transcription and repair..Eur J Biochem2004;271:2335-49

[20] SwygertSG.Chromatin dynamics: interplay between remodeling enzymes and histone modifications..Biochim Biophys Acta - Gene Regul Mech2014;1839:728-36 PMCID:PMC4099280

[21] VignaliM,NeelyKE.ATP-dependent chromatin-remodeling complexes..Mol Cell Biol2000;20:1899-910 PMCID:PMC110808

[22] TyagiM,VermaK.Chromatin remodelers: We are the drivers!!.Nucleus2016;7:388-404 PMCID:PMC5039004

[23] LiW.Architects of the genome: CHD dysfunction in cancer, developmental disorders and neurological syndromes..Epigenomics2014;6:381-95 PMCID:PMC4233650

[24] EissenbergJC.Structural biology of the chromodomain: form and function..Gene2012;496:69-78

[25] HallJA.CHD proteins: a diverse family with strong ties..Biochem Cell Biol2007;85:463-76

[26] DelmasV,PerryRP.A mammalian DNA-binding protein that contains a chromodomain and an SNF2/SWI2-like helicase domain..Proc Natl Acad Sci U S A1993;90:2414-8 PMCID:PMC46097

[27] SanchezR.The PHD finger: a versatile epigenome reader..Trends Biochem Sci2011;36:364-72 PMCID:PMC3130114

[28] XueY,MorenoGT,CôtéJ.NURD, a novel complex with both ATP-dependent chromatin-remodeling and histone deacetylase activities..Mol Cell1998;2:851-61

[29] LamarKMJ.Chromatin remodeling proteins in epilepsy: lessons from CHD2-associated epilepsy..Frontiers in Molecular Neuroscience2018;11:208 PMCID:PMC6013553

[30] ZahirFR.Epigenetic impacts on neurodevelopment: pathophysiological mechanisms and genetic modes of action..Pediatr Res2011;69:92R-100

[31] van LooKMJ.Genetic and environmental factors in complex neurodevelopmental disorders..Curr Genomics2007;8:429-44 PMCID:PMC2647153

[32] ChellyJ,FrancisF,BienvenuT.Genetics and pathophysiology of mental retardation..Eur J Hum Genet2006;14:701-13

[33] ShashiV,RosellB,VelloreK.The utility of the traditional medical genetics diagnostic evaluation in the context of next-generation sequencing for undiagnosed genetic disorders..Genet Med2014;16:176-82

[34] TuckerT,GriffithM,ChaiD.Single exon-resolution targeted chromosomal microarray analysis of known and candidate intellectual disability genes..Eur J Hum Genet2014;22:792-800 PMCID:PMC4023222

[35] ZoghbiHY.Epigenetics and human disease..Cold Spring Harb Perspect Biol2016;8:a019497 PMCID:PMC4743078

[36] Muñoz-NajarU.Epigenetic control of aging..Antioxid Redox Signal2010;14:241-59 PMCID:PMC3014766

[37] ZahirFR,GallK,MarraMA.A novel de novo 1.1 Mb duplication of 17q21.33 associated with cognitive impairment and other anomalies..Am J Med Genet Part A2009;149A:1257-62

[38] Kordi-TamandaniDM,TorkamanzehiA.Analysis of association between dopamine receptor genes’ methylation and their expression profile with the risk of schizophrenia..Psychiatr Genet2013;23:183-7

[39] BastakiKN,ZahirFR.Maternal prenatal exposures in pregnancy and autism spectrum disorder: an insight into the epigenetics of drugs and diet as key environmental influences..Adv Neurobiol2020;24:143-62

[40] BussC,SwansonJM.The role of stress in brain development: the gestational environment’s long-term effects on the brain..Cerebrum2012;2012:4 PMCID:PMC3574809

[41] KundakovicM.The epigenetic link between prenatal adverse environments and neurodevelopmental disorders..Genes (Basel)2017;8:104 PMCID:PMC5368708

[42] MonkC,ChampagneFA.Linking prenatal maternal adversity to developmental outcomes in infants: the role of epigenetic pathways..Dev Psychopathol2012;24:1361-76 PMCID:PMC3730125

[43] KimDR,EppersonCN.Prenatal programming of mental illness: current understanding of relationship and mechanisms..Curr Psychiatry Rep2015;17:5 PMCID:PMC4458064

[44] PereraF.Prenatal environmental exposures, epigenetics, and disease..Reprod Toxicol2011;31:363-73 PMCID:PMC3171169

[45] Breton-LarrivéeM,McGrawS.DNA methylation, environmental exposures and early embryo development..Anim Reprod2019;16:465-74 PMCID:PMC7234019

[46] DulacC.Brain function and chromatin plasticity..Nature2010;465:728-35 PMCID:PMC3075582

[47] HsiehJ.Chromatin remodeling in neural development and plasticity..Curr Opin Cell Biol2005;17:664-71

[48] ShilatifardA.Chromatin modifications by methylation and ubiquitination: implications in the regulation of gene expression..Annu Rev Biochem2006;75:243-69

[49] KleefstraT,NevelingK,KoemansTS.Disruption of an EHMT1-associated chromatin-modification module causes intellectual disability..Am J Hum Genet2012;91:73-82 PMCID:PMC3397275

[50] VissersLELM,AdmiraalR,De VriesBBA.Mutations in a new member of the chromodomain gene family cause CHARGE syndrome..Nat Genet2004;36:955-7

[51] ZahirF,BarossA,EydouxP.Novel deletions of 14q11.2 associated with developmental delay, cognitive impairment and similar minor anomalies in three children..J Med Genet2007;44:556-61 PMCID:PMC2597953

[52] YasinH,LangloisS,TsangES.A distinct neurodevelopmental syndrome with intellectual disability, autism spectrum disorder, characteristic facies, and macrocephaly is caused by defects in CHD8..J Hum Genet2019;64:271-80

[53] KleefstraT,KramerJM.The genetics of cognitive epigenetics..Neuropharmacology2014;80:83-94

[54] PilarowskiGO,ApplegateCD,ChoMT.Missense variants in the chromatin remodeler CHD1 are associated with neurodevelopmental disability..J Med Genet2018;55:561-6 PMCID:PMC5834353

[55] SnijdersBlok L,TwistJ,TakakuM.CHD3 helicase domain mutations cause a neurodevelopmental syndrome with macrocephaly and impaired speech and language..Nat Commun2018;9:4619 PMCID:PMC6218476

[56] SifrimA,WilsdonA,Al TurkiSH.Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing..Nat Genet2016;48:1060-5 PMCID:PMC5988037

[57] CarvillG,MeffordH.AdamMP,PagonRA,BeanLJH,AmemiyaA.CHD2-related neurodevelopmental disorders..2015;SeattleUniversity of Washington

[58] MartinDM.Epigenetic developmental disorders: CHARGE syndrome, a case study..Curr Genet Med Rep2015;3:1-7 PMCID:PMC4325366

[59] HartshorneTS,DavenportSLH.Behavior in CHARGE syndrome: Introduction to the special topic..Am J Med Genet Part A2005;133A:228-31

[60] PagonRA,ZonanaJ.Coloboma, congenital heart disease, and choanal atresia with multiple anomalies: CHARGE association..J Pediatr1981;99:223-7

[61] HotaSK.ATP-dependent chromatin remodeling during mammalian development..Development2016;143:2882-97 PMCID:PMC5004879

[62] DamaschkeNA,BluteML,HuangW.Frequent disruption of chromodomain helicase DNA-binding protein 8 (CHD8) and functionally associated chromatin regulators in prostate cancer..Neoplasia2014;16:1018-27 PMCID:PMC4309256

[63] SawadaG,MatsumuraT,IshibashiM.CHD8 is an independent prognostic indicator that regulates Wnt/β-catenin signaling and the cell cycle in gastric cancer..Oncol Rep2013;30:1137-42

[64] WadeAA,Catta-PretaR.Common CHD8 genomic targets contrast with model-specific transcriptional impacts of CHD8 haploinsufficiency..Front Mol Neurosci2019;11:481 PMCID:PMC6339895

[65] DurakO,Kaeser-WooYJ,MartorellAJ.Chd8 mediates cortical neurogenesis via transcriptional regulation of cell cycle and Wnt signaling..Nat Neurosci2016;19:1477-88 PMCID:PMC5386887

[66] GompersAL,EllegoodJ,RiyadhMA.Germline Chd8 haploinsufficiency alters brain development in mouse..Nat Neurosci2017;20:1062-73 PMCID:PMC6008102

[67] KatayamaY,ShojiH,KawamuraA.CHD8 haploinsufficiency results in autistic-like phenotypes in mice..Nature2016;537:675-9

[68] PlattRJ,SlaymakerIM,WeisbachNR.Chd8 mutation leads to autistic-like behaviors and impaired striatal circuits..Cell Rep2017;19:335-50 PMCID:PMC5455342

[69] SuetterlinP,MohanC,PaganiM.Altered neocortical gene expression, brain overgrowth and functional over-connectivity in Chd8 haploinsufficient mice..Cereb Cortex2018;28:2192-206 PMCID:PMC6018918

[70] JungH,ChoiY,LeeE.Sexually dimorphic behavior, neuronal activity, and gene expression in Chd8-mutant mice..Nat Neurosci2018;21:1218-28

[71] WongWR,MaherS,HoweK.Autism-associated missense genetic variants impact locomotion and neurodevelopment in Caenorhabditis elegans..Hum Mol Genet2019;28:2271-81 PMCID:PMC6586145

[72] GervaisL,JosserandM,StefanuttiM.Stem cell proliferation is kept in check by the chromatin regulators Kismet/CHD7/CHD8 and Trr/MLL3/4..Dev Cell2019;49:556-73.e6 PMCID:PMC6547167

[73] BernierR,XiongB,CoeBP.Disruptive CHD8 mutations define a subtype of autism early in development..Cell2014;158:263-76 PMCID:PMC4136921

[74] SugathanA,GolzioC,BlumenthalI.CHD8 regulates neurodevelopmental pathways associated with autism spectrum disorder in neural progenitors..Proc Natl Acad Sci2014;111:E4468-77 PMCID:PMC4210312

[75] WangP,PedrosaE,BayrakC.CRISPR/Cas9-mediated heterozygous knockout of the autism gene CHD8 and characterization of its transcriptional networks in cerebral organoids derived from iPS cells..Mol Autism2017;8:1-17 PMCID:PMC5357816

[76] WangP,PedrosaE,BayrakC.CRISPR/Cas9-mediated heterozygous knockout of the autism gene CHD8 and characterization of its transcriptional networks in cerebral organoids derived from iPS cells..Mol Autism2015;8:1-18

[77] WilkinsonB,ThompsonBL,WangK.The autism-associated gene chromodomain helicase DNA-binding protein 8 (CHD8) regulates noncoding RNAs and autism-related genes..Transl Psychiatry2015;5: PMCID:PMC4471293

[78] MarianiJ,ZhangP,ProviniL.FOXG1-dependent dysregulation of GABA/glutamate neuron differentiation in autism spectrum disorders..Cell2015;162:375-90 PMCID:PMC4519016

[79] KitaY,ShiraishiT,SatoT.The autism-related protein CHD8 cooperates with C/EBPβ to regulate adipogenesis..Cell Rep2018;23:1988-2000

[80] KawamuraA,NishiyamaM,TokuokaK.Oligodendrocyte dysfunction due to Chd8 mutation gives rise to behavioral deficits in mice..Hum Mol Genet2020;29:1274-91

[81] WeissK,CohenL,IrvingM.De Novo Mutations in CHD4, an ATP-dependent chromatin remodeler gene, cause an intellectual disability syndrome with distinctive dysmorphisms..Am J Hum Genet2016;99:934-41 PMCID:PMC5065651

[82] BergmanJE,HoefslootLH,HofstraRM.CHD7 mutations and CHARGE syndrome: the clinical implications of an expanding phenotype..J Med Genet2011;48:334-42