title: Cytosine modifications in neurodevelopment and diseases.
abstract: DNA methylation has been studied comprehensively and linked to both normal neurodevelopment and neurological diseases. The recent identification of several new DNA modifications, including 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine, has given us a new perspective on the previously observed plasticity in 5mC-dependent regulatory processes. Here, we review the latest research into these cytosine modifications, focusing mainly on their roles in neurodevelopment and diseases.
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Suite 301, Atlanta, GA, 30322, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Yao
authors.forename: Peng
authors.initials: P
authors.lastname: Jin
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D019175:DNA Methylation / Q000502:physiology*; D015257:DNA-Cytosine Methylases / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D009422:Nervous System Diseases / Q000503:physiopathology*; D055495:Neurogenesis / Q000502:physiology*
chemical_list: C560974:5-carboxylcytosine; C560973:5-formylcytosine; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine; D015257:DNA-Cytosine Methylases
references.citation: Science. 2007 Feb 23;315(5815):1143-7
references.pmid: 17289941
references.citation: Nat Rev Cancer. 2011 Sep 23;11(10):726-34
references.pmid: 21941284
references.citation: Nat Rev Genet. 2010 Apr;11(4):247-58
references.pmid: 20177426
references.citation: Semin Reprod Med. 2009 Sep;27(5):351-7
references.pmid: 19711245
references.citation: Proc Natl Acad Sci U S A. 1999 Dec 7;96(25):14412-7
references.pmid: 10588719
references.citation: Nat Genet. 2011 Jun;43(6):595-600
references.pmid: 21532572
references.citation: Nat Rev Genet. 2002 Jun;3(6):415-28
references.pmid: 12042769
references.citation: Biochem J. 1972 Feb;126(4):781-90
references.pmid: 4538516
references.citation: Clin Genet. 2008 Aug;74(2):116-26
references.pmid: 18477000
references.citation: Nature. 2007 Feb 8;445(7128):671-5
references.pmid: 17268471
references.citation: Neuron. 2007 Aug 16;55(4):565-71
references.pmid: 17698010
references.citation: Cell. 2012 Dec 21;151(7):1417-30
references.pmid: 23260135
references.citation: Nat Rev Genet. 2005 Aug;6(8):597-610
references.pmid: 16136652
references.citation: Nat Rev Genet. 2011 Nov 15;13(1):7-13
references.pmid: 22083101
references.citation: Mol Cell. 2011 May 20;42(4):451-64
references.pmid: 21514197
references.citation: Nature. 2011 Sep 04;477(7366):606-10
references.pmid: 21892189
references.citation: Nat Rev Genet. 2002 Sep;3(9):662-73
references.pmid: 12209141
references.citation: Science. 2008 May 30;320(5880):1224-9
references.pmid: 18511691
references.citation: Nature. 2011 May 19;473(7347):394-7
references.pmid: 21552279
references.citation: Nature. 1969 Aug 9;223(5206):580-2
references.pmid: 5799529
references.citation: Nature. 2013 Mar 21;495(7441):370-4
references.pmid: 23395962
references.citation: Science. 2009 May 15;324(5929):929-30
references.pmid: 19372393
references.citation: Nat Genet. 2005 Jan;37(1):31-40
references.pmid: 15608638
references.citation: Blood. 2012 Jan 12;119(2):559-68
references.pmid: 22077061
references.citation: PLoS Genet. 2011 Jun;7(6):e1002154
references.pmid: 21731508
references.citation: Cell. 1992 Jun 12;69(6):915-26
references.pmid: 1606615
references.citation: Cell. 2012 Dec 7;151(6):1200-13
references.pmid: 23217707
references.citation: Mol Cell. 2010 Feb 26;37(4):457-68
references.pmid: 20188665
references.citation: Cell. 1991 Mar 22;64(6):1123-34
references.pmid: 2004419
references.citation: Neuron. 2011 Oct 6;72(1):72-85
references.pmid: 21982370
references.citation: Cell. 2013 Apr 25;153(3):692-706
references.pmid: 23602152
references.citation: Science. 2011 Sep 2;333(6047):1303-7
references.pmid: 21817016
references.citation: Neuron. 2007 Aug 16;55(4):556-64
references.pmid: 17698009
references.citation: Angew Chem Int Ed Engl. 2011 Jul 25;50(31):7008-12
references.pmid: 21721093
references.citation: Nat Genet. 2000 Feb;24(2):132-8
references.pmid: 10655057
references.citation: N Engl J Med. 2010 Dec 16;363(25):2424-33
references.pmid: 21067377
references.citation: Cell. 2011 Apr 29;145(3):423-34
references.pmid: 21496894
references.citation: Cell. 1997 Feb 21;88(4):471-81
references.pmid: 9038338
references.citation: Cell Stem Cell. 2011 Aug 5;9(2):166-75
references.pmid: 21816367
references.citation: Nature. 2000 Feb 3;403(6769):501-2
references.pmid: 10676950
references.citation: Cell. 2012 Jun 8;149(6):1368-80
references.pmid: 22608086
references.citation: Mol Cell. 2013 Feb 21;49(4):645-56
references.pmid: 23352454
references.citation: Lancet Neurol. 2009 Nov;8(11):1056-72
references.pmid: 19833297
references.citation: Nature. 2006 Jun 29;441(7097):1087-93
references.pmid: 16810244
references.citation: Science. 2013 Mar 29;339(6127):1621-5
references.pmid: 23393090
references.citation: Nature. 2007 May 24;447(7143):425-32
references.pmid: 17522676
references.citation: Am J Hum Genet. 2011 Jun 10;88(6):796-804
references.pmid: 21596365
references.citation: Nature. 2013 Jan 24;493(7433):561-4
references.pmid: 23222540
references.citation: N Engl J Med. 2008 Mar 13;358(11):1148-59
references.pmid: 18337604
references.citation: Brief Funct Genomics. 2013 May;12(3):174-90
references.pmid: 23341493
references.citation: Curr Biol. 2000 Apr 20;10(8):475-8
references.pmid: 10801417
references.citation: Hum Mol Genet. 2008 Mar 1;17(5):690-709
references.pmid: 18029387
references.citation: Nat Cell Biol. 2004 Nov;6(11):1048-53
references.pmid: 15516998
references.citation: Nat Rev Genet. 2005 Oct;6(10):743-55
references.pmid: 16205714
references.citation: Hum Mol Genet. 2013 Sep 15;22(18):3641-53
references.pmid: 23669348
references.citation: EMBO Rep. 2011 Dec 23;13(1):28-35
references.pmid: 22157888
references.citation: J Biol Chem. 2013 May 10;288(19):13669-74
references.pmid: 23548903
references.citation: Hum Mol Genet. 2002 Jan 15;11(2):115-24
references.pmid: 11809720
references.citation: Chromosoma. 2009 Oct;118(5):549-65
references.pmid: 19506892
references.citation: Nature. 2010 Aug 26;466(7310):1129-33
references.pmid: 20639862
references.citation: Nat Med. 2012 Aug;18(8):1194-204
references.pmid: 22869198
references.citation: Neuron. 2007 Nov 8;56(3):422-37
references.pmid: 17988628
references.citation: Science. 2013 Jan 25;339(6118):448-52
references.pmid: 23223451
references.citation: Nature. 2010 Dec 9;468(7325):839-43
references.pmid: 21057493
references.citation: Cell. 1999 Oct 29;99(3):247-57
references.pmid: 10555141
references.citation: Cell. 2002 Dec 13;111(6):771-8
references.pmid: 12526804
references.citation: Nature. 1999 Nov 11;402(6758):187-91
references.pmid: 10647011
references.citation: Cell. 2013 Feb 28;152(5):1146-59
references.pmid: 23434322
references.citation: Nature. 2012 Aug 30;488(7413):652-5
references.pmid: 22902501
references.citation: Thalamus Relat Syst. 2005 Sep;3(3):227-233
references.pmid: 17710197
references.citation: Cell. 2007 Feb 23;128(4):683-92
references.pmid: 17320506
references.citation: Mutat Res. 2008 Dec 1;647(1-2):30-8
references.pmid: 18778722
references.citation: J Neurosci Res. 2005 Mar 15;79(6):734-46
references.pmid: 15672446
references.citation: Science. 1991 May 24;252(5009):1097-102
references.pmid: 2031184
references.citation: Nat Genet. 1999 Oct;23(2):185-8
references.pmid: 10508514
references.citation: Clin Cancer Res. 2012 May 1;18(9):2490-501
references.pmid: 22415316
references.citation: Cell. 2013 Apr 25;153(3):678-91
references.pmid: 23602153
references.citation: Cell. 2012 Sep 14;150(6):1135-46
references.pmid: 22980977
references.citation: Nat Neurosci. 2011 Oct 30;14(12):1607-16
references.pmid: 22037496
references.citation: Neuron. 2006 Oct 19;52(2):255-69
references.pmid: 17046689
references.citation: Dev Biol. 2009 Oct 1;334(1):213-23
references.pmid: 19631206
references.citation: Science. 2009 May 15;324(5929):930-5
references.pmid: 19372391
references.citation: Mol Cell Biol. 1998 Nov;18(11):6538-47
references.pmid: 9774669
references.citation: Cell Rep. 2013 Feb 21;3(2):291-300
references.pmid: 23403289
references.citation: Cell Stem Cell. 2011 Sep 2;9(3):193-204
references.pmid: 21885017
references.citation: Cancer Cell. 2011 Jul 12;20(1):11-24
references.pmid: 21723200
references.citation: Nat Biotechnol. 2011 Jan;29(1):68-72
references.pmid: 21151123
references.citation: Annu Rev Cell Dev Biol. 2011;27:631-52
references.pmid: 21721946
references.citation: Dev Cell. 2013 Feb 11;24(3):310-23
references.pmid: 23352810
references.citation: FEBS Lett. 2001 Apr 13;494(3):135-40
references.pmid: 11311228
references.citation: Differentiation. 1994 Apr;56(1-2):39-44
references.pmid: 8026645
references.citation: Genes Dev. 2004 May 1;18(9):1035-46
references.pmid: 15105378
references.citation: Hum Mol Genet. 2012 May 15;21(10):2205-10
references.pmid: 22328086
references.citation: Nucleic Acids Res. 2012 Jun;40(11):4841-9
references.pmid: 22362737
references.citation: Nat Chem Biol. 2012 Feb 12;8(4):328-30
references.pmid: 22327402
references.citation: Cell Res. 2011 Dec;21(12):1670-6
references.pmid: 22124233
references.citation: Nat Neurosci. 2010 Nov;13(11):1338-44
references.pmid: 20975758
references.citation: Proc Natl Acad Sci U S A. 2003 May 27;100(11):6777-82
references.pmid: 12748381
references.citation: Angew Chem Int Ed Engl. 2010 Jul 19;49(31):5375-7
references.pmid: 20583021
references.citation: Nat Genet. 2003 Mar;33 Suppl:245-54
references.pmid: 12610534
references.citation: Cell. 2011 Dec 23;147(7):1498-510
references.pmid: 22196727
references.citation: Science. 2009 Feb 20;323(5917):1074-7
references.pmid: 19119186
references.citation: Cancer Cell. 2011 Jan 18;19(1):17-30
references.pmid: 21251613
references.citation: Development. 2005 Aug;132(15):3345-56
references.pmid: 16014513
references.citation: EMBO J. 2013 Mar 6;32(5):645-55
references.pmid: 23353889
references.citation: Neuron. 2007 Mar 15;53(6):857-69
references.pmid: 17359920
references.citation: Proc Natl Acad Sci U S A. 2005 Dec 6;102(49):17551-8
references.pmid: 16251272
references.citation: Epigenetics. 2006 Apr-Jun;1(2):76-80
references.pmid: 17998809
references.citation: Development. 2012 Jun;139(11):1895-902
references.pmid: 22569552
references.citation: Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):1931-6
references.pmid: 17267601
references.citation: PLoS One. 2012;7(8):e43724
references.pmid: 22928023
references.citation: Cell Stem Cell. 2013 Apr 4;12(4):470-8
references.pmid: 23415914
references.citation: Cytogenet Genome Res. 2003;100(1-4):25-55
references.pmid: 14526163
references.citation: Clin Genet. 2012 Nov;82(5):489-93
references.pmid: 21906047
references.citation: Proc Natl Acad Sci U S A. 2011 Aug 30;108(35):14566-71
references.pmid: 21873190
references.citation: Hum Mol Genet. 2000 Oct;9(16):2395-402
references.pmid: 11005794
references.citation: Nature. 2005 Jun 16;435(7044):903-10
references.pmid: 15959507
references.citation: Nat Rev Genet. 2008 Jun;9(6):465-76
references.pmid: 18463664
references.citation: Cell Stem Cell. 2011 Feb 4;8(2):200-13
references.pmid: 21295276
references.citation: Cell. 1992 Jun 12;69(6):905-14
references.pmid: 1606614
references.citation: Hum Mol Genet. 2009 Jul 1;18(13):2431-42
references.pmid: 19369296
references.citation: Dev Neurobiol. 2009 Feb 1-15;69(2-3):162-73
references.pmid: 19086029
references.citation: J Biol Chem. 2008 Oct 10;283(41):27644-27652
references.pmid: 18689796
references.citation: Br J Cancer. 2008 Jun 17;98(12):1881-5
references.pmid: 18542062
references.citation: Proc Natl Acad Sci U S A. 2013 Feb 5;110(6):2354-9
references.pmid: 23341638
references.citation: Nature. 2009 Aug 27;460(7259):1127-31
references.pmid: 19657334
references.citation: Nat Neurosci. 2010 Apr;13(4):423-30
references.pmid: 20228804
references.citation: Science. 2011 Sep 2;333(6047):1300-3
references.pmid: 21778364
references.citation: Dev Dyn. 2007 Jun;236(6):1663-76
references.pmid: 17477386
references.citation: Ann Neurol. 2009 Dec;66(6):771-82
references.pmid: 20035514
references.citation: Biochem J. 1953 Dec;55(5):774-82
references.pmid: 13115372
references.citation: Science. 2010 Jul 23;329(5990):444-8
references.pmid: 20651149
references.citation: Nat Rev Cancer. 2010 Jul;10(7):457-69
references.pmid: 20574448
references.citation: Blood. 2013 Apr 11;121(15):2988-95
references.pmid: 23365461
references.citation: Cell. 1991 May 31;65(5):905-14
references.pmid: 1710175
references.citation: Nature. 2011 May 19;473(7347):343-8
references.pmid: 21490601
references.citation: Mamm Genome. 1995 Aug;6(8):491-2
references.pmid: 8589515
references.citation: EMBO Rep. 2004 Dec;5(12):1181-6
references.pmid: 15550930