Evolution of DNA methylation in the human brain.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
01 04 2021
01 04 2021
Historique:
received:
07
09
2020
accepted:
16
02
2021
entrez:
2
4
2021
pubmed:
3
4
2021
medline:
20
4
2021
Statut:
epublish
Résumé
DNA methylation is a critical regulatory mechanism implicated in development, learning, memory, and disease in the human brain. Here we have elucidated DNA methylation changes during recent human brain evolution. We demonstrate dynamic evolutionary trajectories of DNA methylation in cell-type and cytosine-context specific manner. Specifically, DNA methylation in non-CG context, namely CH methylation, has increased (hypermethylation) in neuronal gene bodies during human brain evolution, contributing to human-specific down-regulation of genes and co-expression modules. The effects of CH hypermethylation is particularly pronounced in early development and neuronal subtypes. In contrast, DNA methylation in CG context shows pronounced reduction (hypomethylation) in human brains, notably in cis-regulatory regions, leading to upregulation of downstream genes. We show that the majority of differential CG methylation between neurons and oligodendrocytes originated before the divergence of hominoids and catarrhine monkeys, and harbors strong signal for genetic risk for schizophrenia. Remarkably, a substantial portion of differential CG methylation between neurons and oligodendrocytes emerged in the human lineage since the divergence from the chimpanzee lineage and carries significant genetic risk for schizophrenia. Therefore, recent epigenetic evolution of human cortex has shaped the cellular regulatory landscape and contributed to the increased vulnerability to neuropsychiatric diseases.
Identifiants
pubmed: 33795684
doi: 10.1038/s41467-021-21917-7
pii: 10.1038/s41467-021-21917-7
pmc: PMC8017017
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
2021Subventions
Organisme : NINDS NIH HHS
ID : R24 NS092988
Pays : United States
Références
Nature. 2019 Sep;573(7772):61-68
pubmed: 31435019
Genome Biol Evol. 2017 Nov 1;9(11):3189-3201
pubmed: 29036466
Genome Biol. 2014 Mar 04;15(3):R49
pubmed: 24594098
Science. 2016 Oct 28;354(6311):477-481
pubmed: 27789843
Nature. 2011 Mar 3;471(7336):68-73
pubmed: 21289626
Cell. 2017 Nov 16;171(5):1151-1164.e16
pubmed: 29056337
Genome Biol. 2019 Sep 26;20(1):196
pubmed: 31554518
Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):13030-5
pubmed: 14557539
Hum Mol Genet. 2016 Jan 1;25(1):69-82
pubmed: 26512062
Nat Neurosci. 2017 Oct;20(10):1418-1426
pubmed: 28869584
Nat Neurosci. 2019 Feb;22(2):307-316
pubmed: 30643296
J Anat. 2008 Apr;212(4):426-54
pubmed: 18380864
Methods. 2002 Jun;27(2):101-7
pubmed: 12095266
Neuron. 2012 Aug 23;75(4):601-17
pubmed: 22920253
Nature. 2007 Jan 11;445(7124):168-76
pubmed: 17151600
Philos Trans R Soc Lond B Biol Sci. 2013 Nov 11;368(1632):20130025
pubmed: 24218637
Nat Rev Neurosci. 2006 Sep;7(9):687-96
pubmed: 16883309
Cancer Inform. 2019 Feb 11;18:1176935119828776
pubmed: 30792573
Science. 2018 Dec 14;362(6420):
pubmed: 30545855
Genome Res. 2010 Sep;20(9):1297-303
pubmed: 20644199
BMC Evol Biol. 2008 Jan 23;8:17
pubmed: 18215302
Nat Neurosci. 2016 Mar;19(3):494-503
pubmed: 26807951
Nature. 2020 May;581(7809):434-443
pubmed: 32461654
Genome Biol. 2011 Jun 22;12(6):R58
pubmed: 21696599
Science. 2013 Aug 9;341(6146):1237905
pubmed: 23828890
Am J Hum Genet. 2019 Apr 4;104(4):611-624
pubmed: 30905396
Am J Hum Genet. 2012 Sep 7;91(3):455-65
pubmed: 22922032
Nat Med. 2012 Aug;18(8):1194-204
pubmed: 22869198
Cell. 2017 Jul 13;170(2):226-247
pubmed: 28708995
Mol Biol Evol. 2008 Dec;25(12):2699-707
pubmed: 18820252
Nature. 2017 Oct 11;550(7675):204-213
pubmed: 29022597
Genome Biol. 2019 Jul 9;20(1):135
pubmed: 31288836
Nucleic Acids Res. 2016 Apr 7;44(6):2593-612
pubmed: 26612861
PLoS Genet. 2006 Oct 6;2(10):e163
pubmed: 17029560
Nature. 2011 Oct 12;478(7370):476-82
pubmed: 21993624
Bioinformatics. 2016 May 15;32(10):1446-53
pubmed: 26819470
Genome Res. 2018 Aug;28(8):1243-1252
pubmed: 29945882
Nucleic Acids Res. 2016 Jan 4;44(D1):D116-25
pubmed: 26586801
Nat Genet. 2013 Oct;45(10):1198-206
pubmed: 23995138
Nat Rev Genet. 2008 Oct;9(10):749-63
pubmed: 18802414
Nat Genet. 2015 Nov;47(11):1228-35
pubmed: 26414678
Ann N Y Acad Sci. 2011 May;1225 Suppl 1:E182-91
pubmed: 21599696
Nat Methods. 2012 Mar 04;9(4):357-9
pubmed: 22388286
PLoS Genet. 2011 Dec;7(12):e1002389
pubmed: 22174693
Genetica. 2007 Oct;131(2):151-6
pubmed: 17160620
Nucleic Acids Res. 2018 Jan 4;46(D1):D754-D761
pubmed: 29155950
Genome Biol. 2007;8(6):R118
pubmed: 17578567
Sci Adv. 2018 Sep 26;4(9):eaau6190
pubmed: 30263963
Nat Biotechnol. 2010 May;28(5):495-501
pubmed: 20436461
Science. 2006 Nov 3;314(5800):786
pubmed: 17082449
Nat Rev Genet. 2004 Nov;5(11):850-60
pubmed: 15520794
Nature. 2016 Oct 27;538(7626):523-527
pubmed: 27760116
PLoS Biol. 2012;10(11):e1001427
pubmed: 23185133
Bioinformatics. 2011 Jun 1;27(11):1571-2
pubmed: 21493656
Mol Biol Evol. 2016 Nov;33(11):2947-2959
pubmed: 27563052
Nat Commun. 2020 Nov 4;11(1):5581
pubmed: 33149216
Nat Genet. 1996 Mar;12(3):260-5
pubmed: 8589716
Nat Genet. 2018 Apr;50(4):621-629
pubmed: 29632380
Nat Neurosci. 2018 Aug;21(8):1126-1136
pubmed: 30038276
Genome Res. 2020 May;30(5):776-789
pubmed: 32424074
Proc Natl Acad Sci U S A. 2019 Nov 26;116(48):24334-24342
pubmed: 31712436
Nucleic Acids Res. 2014 Apr;42(8):e69
pubmed: 24561809
Genome Res. 2015 Mar;25(3):338-52
pubmed: 25650246
Nucleic Acids Res. 2009 Jul;37(Web Server issue):W202-8
pubmed: 19458158
Nat Commun. 2020 Jan 16;11(1):301
pubmed: 31949148
Nature. 2015 Jan 15;517(7534):321-6
pubmed: 25592537
PLoS Comput Biol. 2008 Feb 29;4(2):e1000015
pubmed: 18463707
Science. 2017 Aug 11;357(6351):600-604
pubmed: 28798132
Genome Biol Evol. 2010 Jan 18;2:67-79
pubmed: 20333225