MicroRNA-29 is an essential regulator of brain maturation through regulation of CH methylation.
3' Untranslated Regions
/ genetics
Animals
Animals, Newborn
Base Sequence
Behavior, Animal
Brain
/ growth & development
DNA (Cytosine-5-)-Methyltransferases
/ metabolism
DNA Methylation
/ genetics
Down-Regulation
/ genetics
Gene Expression Regulation, Developmental
Mice, Inbred C57BL
MicroRNAs
/ genetics
Neurodevelopmental Disorders
/ genetics
Neurons
/ metabolism
Seizures
/ genetics
Signal Transduction
Synapses
/ metabolism
Up-Regulation
/ genetics
CH methylation
DNMT3A
MeCP2
autism
epilepsy
miR-29
miRNA
neurodevelopmental disorders
non-CG methylation
seizures
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
06 04 2021
06 04 2021
Historique:
received:
28
07
2020
revised:
09
12
2020
accepted:
14
03
2021
entrez:
7
4
2021
pubmed:
8
4
2021
medline:
27
1
2022
Statut:
ppublish
Résumé
Although embryonic brain development and neurodegeneration have received considerable attention, the events that govern postnatal brain maturation are less understood. Here, we identify the miR-29 family to be strikingly induced during the late stages of brain maturation. Brain maturation is associated with a transient, postnatal period of de novo non-CG (CH) DNA methylation mediated by DNMT3A. We examine whether an important function of miR-29 during brain maturation is to restrict the period of CH methylation via its targeting of Dnmt3a. Deletion of miR-29 in the brain, or knockin mutations preventing miR-29 to specifically target Dnmt3a, result in increased DNMT3A expression, higher CH methylation, and repression of genes associated with neuronal activity and neuropsychiatric disorders. These mouse models also develop neurological deficits and premature lethality. Our results identify an essential role for miR-29 in restricting CH methylation in the brain and illustrate the importance of CH methylation regulation for normal brain maturation.
Identifiants
pubmed: 33826889
pii: S2211-1247(21)00260-6
doi: 10.1016/j.celrep.2021.108946
pmc: PMC8103628
mid: NIHMS1691239
pii:
doi:
Substances chimiques
3' Untranslated Regions
0
MIRN29 microRNA, mouse
0
MicroRNAs
0
DNA (Cytosine-5-)-Methyltransferases
EC 2.1.1.37
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
108946Subventions
Organisme : NCI NIH HHS
ID : U54 CA156733
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES010126
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM118331
Pays : United States
Organisme : NICHD NIH HHS
ID : P50 HD103573
Pays : United States
Organisme : NINDS NIH HHS
ID : P30 NS045892
Pays : United States
Organisme : NINDS NIH HHS
ID : R35 NS116859
Pays : United States
Organisme : NIEHS NIH HHS
ID : P42 ES031007
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD098657
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016086
Pays : United States
Organisme : NICHD NIH HHS
ID : U54 HD079124
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG055304
Pays : United States
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
Références
Stem Cell Res. 2014 Mar;12(2):550-61
pubmed: 24530979
Nat Genet. 2012 Jan 08;44(2):206-11
pubmed: 22231481
Front Neurosci. 2016 May 10;10:192
pubmed: 27242398
Nature. 2006 Jan 19;439(7074):283-9
pubmed: 16421561
Proc Natl Acad Sci U S A. 2008 Apr 29;105(17):6415-20
pubmed: 18434550
Curr Psychiatry Rep. 2015 May;17(5):32
pubmed: 25773225
Science. 2017 Aug 11;357(6351):600-604
pubmed: 28798132
Physiol Genomics. 2012 Feb 27;44(4):237-44
pubmed: 22214600
Lancet Neurol. 2016 Mar;15(3):304-16
pubmed: 26597089
Exp Cell Res. 2014 Feb 1;321(1):84-9
pubmed: 24099990
Nat Neurosci. 2019 Feb;22(2):307-316
pubmed: 30643296
Int J Clin Exp Pathol. 2015 Feb 01;8(2):1565-74
pubmed: 25973041
J Clin Med. 2019 Jan 14;8(1):
pubmed: 30646527
Biol Psychiatry. 2015 Aug 15;78(4):231-9
pubmed: 25636176
BMC Bioinformatics. 2009 Jul 27;10:232
pubmed: 19635165
Cell. 2012 Feb 17;148(4):816-31
pubmed: 22341451
Science. 2008 May 30;320(5880):1224-9
pubmed: 18511691
Genome Biol. 2009;10(3):R25
pubmed: 19261174
Nat Genet. 2014 Apr;46(4):385-8
pubmed: 24614070
Trends Neurosci. 2011 Mar;34(3):134-42
pubmed: 21315459
Mol Cell. 2007 Jul 6;27(1):91-105
pubmed: 17612493
Nat Genet. 2008 Jun;40(6):751-60
pubmed: 18469815
J Biotechnol. 2011 Mar 20;152(3):96-101
pubmed: 21295623
Neurosci Lett. 2015 Mar 17;590:40-6
pubmed: 25625222
Prog Neurobiol. 2019 Nov;182:101664
pubmed: 31356849
Genome Biol. 2014;15(12):550
pubmed: 25516281
RNA. 2011 Aug;17(8):1489-501
pubmed: 21712401
Annu Rev Genomics Hum Genet. 2015;16:55-77
pubmed: 26077819
Science. 2013 Aug 9;341(6146):1237905
pubmed: 23828890
Nature. 2015 Jun 4;522(7554):89-93
pubmed: 25762136
Neuropsychol Rev. 2010 Dec;20(4):327-48
pubmed: 21042938
Hum Mol Genet. 2004 Nov 1;13(21):2679-89
pubmed: 15351775
Trends Cell Biol. 2013 Jan;23(1):30-6
pubmed: 23026030
Mol Psychiatry. 2010 Dec;15(12):1176-89
pubmed: 19721432
Protein Cell. 2014 Feb;5(2):160-9
pubmed: 24535747
Nucleic Acids Res. 2019 Jul 2;47(W1):W191-W198
pubmed: 31066453
Nat Neurosci. 2015 Jul;18(7):1008-16
pubmed: 26005852
Curr Opin Neurobiol. 2019 Dec;59:180-188
pubmed: 31542590
RNA. 2014 Aug;20(8):1287-97
pubmed: 24958907
Front Mol Neurosci. 2017 Nov 09;10:350
pubmed: 29170626
Sci Rep. 2017 Jul 14;7(1):5411
pubmed: 28710399
Nucleic Acids Res. 2017 Jan 4;45(D1):D833-D839
pubmed: 27924018
Proc Natl Acad Sci U S A. 2015 Jun 2;112(22):6800-6
pubmed: 25739960
Oncogene. 2015 Jan 15;34(3):394-402
pubmed: 24469054
Cell Rep. 2016 Dec 20;17(12):3369-3384
pubmed: 28009303
Mol Neurobiol. 2018 Mar;55(3):2483-2493
pubmed: 28386848
J Cell Biochem. 2016 Jan;117(1):29-38
pubmed: 26205787
J Neurosci Res. 2005 Mar 15;79(6):734-46
pubmed: 15672446
J Biol Chem. 2018 May 11;293(19):7344-7354
pubmed: 29567833
Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15805-10
pubmed: 17890317
PLoS One. 2013 Sep 09;8(9):e73240
pubmed: 24039891
Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):3125-30
pubmed: 22315408
Neurobiol Dis. 2015 Jan;73:275-88
pubmed: 25315682
Neuropsychopharmacology. 2013 Jan;38(1):23-38
pubmed: 22781841
Neuron. 2015 Jun 17;86(6):1369-84
pubmed: 26087164
Neuron. 2010 Feb 11;65(3):373-84
pubmed: 20159450
Nucleic Acids Res. 2011 Jan;39(Database issue):D561-8
pubmed: 21045058
J Clin Invest. 2015 Aug 3;125(8):2914-23
pubmed: 26237041
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Proc Natl Acad Sci U S A. 2015 Apr 28;112(17):5509-14
pubmed: 25870282
Anal Biochem. 2014 Oct 1;462:32-4
pubmed: 24929089
Trends Cogn Sci. 2017 Oct;21(10):760-778
pubmed: 28754595
NPJ Genom Med. 2016 Aug 3;1:160271-1602710
pubmed: 27525107
J Biol Chem. 2011 Apr 1;286(13):11837-48
pubmed: 21310958
Stem Cell Reports. 2017 Aug 8;9(2):571-586
pubmed: 28757169
FEBS Lett. 2013 Mar 18;587(6):775-81
pubmed: 23399934
Nat Rev Neurosci. 2015 Sep;16(9):551-63
pubmed: 26289574
Cell. 2017 Nov 16;171(5):1151-1164.e16
pubmed: 29056337
Nucleic Acids Res. 2018 Jan 4;46(D1):D649-D655
pubmed: 29145629
PLoS One. 2012;7(5):e35921
pubmed: 22615744
Proc Natl Acad Sci U S A. 2017 Apr 4;114(14):E2882-E2890
pubmed: 28320934
Bioinformatics. 2009 Aug 15;25(16):2078-9
pubmed: 19505943
Nat Methods. 2017 Apr;14(4):417-419
pubmed: 28263959
Nucleic Acids Res. 2006 Jan 1;34(Database issue):D140-4
pubmed: 16381832
Exp Neurol. 2015 Jun;268:46-53
pubmed: 25128264
Trends Neurosci. 2006 Mar;29(3):148-59
pubmed: 16472876
Nat Rev Dis Primers. 2017 Sep 29;3:17065
pubmed: 28960184
BMC Biol. 2017 Feb 13;15(1):9
pubmed: 28193224
Biol Psychiatry. 2011 Jan 15;69(2):180-7
pubmed: 21111402
J Cereb Blood Flow Metab. 2013 Aug;33(8):1197-206
pubmed: 23632968
Neurobiol Dis. 2016 Aug;92(Pt A):3-17
pubmed: 26184894
Front Cell Neurosci. 2019 Dec 05;13:536
pubmed: 31866828
PLoS One. 2013;8(3):e58039
pubmed: 23516428
Nat Neurosci. 2014 Feb;17(2):215-22
pubmed: 24362762