Developmental regulation of DNA cytosine methylation at the immunoglobulin heavy chain constant locus.
Animals
B-Lymphocytes
/ cytology
Cell Lineage
/ genetics
CpG Islands
/ genetics
Cytosine
/ metabolism
DNA Methylation
Epigenesis, Genetic
Gene Expression Regulation, Developmental
Genes, Immunoglobulin Heavy Chain
Immunoglobulin Constant Regions
/ genetics
Immunoglobulin Heavy Chains
/ genetics
Lymphocyte Activation
/ genetics
Mice
Promoter Regions, Genetic
Journal
PLoS genetics
ISSN: 1553-7404
Titre abrégé: PLoS Genet
Pays: United States
ID NLM: 101239074
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
11
10
2018
accepted:
03
01
2019
entrez:
20
2
2019
pubmed:
20
2
2019
medline:
16
4
2019
Statut:
epublish
Résumé
DNA cytosine methylation is involved in the regulation of gene expression during development and its deregulation is often associated with disease. Mammalian genomes are predominantly methylated at CpG dinucleotides. Unmethylated CpGs are often associated with active regulatory sequences while methylated CpGs are often linked to transcriptional silencing. Previous studies on CpG methylation led to the notion that transcription initiation is more sensitive to CpG methylation than transcriptional elongation. The immunoglobulin heavy chain (IgH) constant locus comprises multiple inducible constant genes and is expressed exclusively in B lymphocytes. The developmental B cell stage at which methylation patterns of the IgH constant genes are established, and the role of CpG methylation in their expression, are unknown. Here, we find that methylation patterns at most cis-acting elements of the IgH constant genes are established and maintained independently of B cell activation or promoter activity. Moreover, one of the promoters, but not the enhancers, is hypomethylated in sperm and early embryonic cells, and is targeted by different demethylation pathways, including AID, UNG, and ATM pathways. Combined, the data suggest that, rather than being prominently involved in the regulation of the IgH constant locus expression, DNA methylation may primarily contribute to its epigenetic pre-marking.
Identifiants
pubmed: 30779742
doi: 10.1371/journal.pgen.1007930
pii: PGENETICS-D-18-01988
pmc: PMC6380546
doi:
Substances chimiques
Immunoglobulin Constant Regions
0
Immunoglobulin Heavy Chains
0
Cytosine
8J337D1HZY
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1007930Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
J Biol Chem. 2016 Jan 8;291(2):731-8
pubmed: 26620559
Nature. 2012 Oct 25;490(7421):561-5
pubmed: 23023124
Blood. 2010 Sep 16;116(11):1895-8
pubmed: 20538806
Genes Dev. 2017 May 15;31(10):959-972
pubmed: 28607180
Proc Natl Acad Sci U S A. 2015 Oct 13;112(41):12776-81
pubmed: 26417104
Mol Immunol. 1992 Sep;29(9):1105-12
pubmed: 1379679
Proc Natl Acad Sci U S A. 2007 Jul 24;104(30):12377-82
pubmed: 17640912
Adv Immunol. 2000;75:317-45
pubmed: 10879288
Gene. 1988 May 30;65(2):219-27
pubmed: 2842233
EMBO J. 2011 Apr 20;30(8):1608-20
pubmed: 21378751
EMBO J. 1992 Jan;11(1):145-55
pubmed: 1740102
Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3843-8
pubmed: 18292225
Proc Natl Acad Sci U S A. 1983 Nov;80(21):6642-6
pubmed: 6314334
Genes Dev. 2009 Dec 15;23(24):2824-38
pubmed: 20008934
Mol Cell. 2001 Sep;8(3):719-25
pubmed: 11583633
EMBO J. 1986 Jan;5(1):95-102
pubmed: 3007121
Nat Commun. 2015 Oct 19;6:8324
pubmed: 26477271
Epigenetics Chromatin. 2013 Nov 14;6(1):39
pubmed: 24279473
Genes Dev. 2009 Dec 15;23(24):2793-8
pubmed: 20008929
Nature. 2010 Feb 25;463(7284):1101-5
pubmed: 20098412
Proc Natl Acad Sci U S A. 2017 Jun 6;114(23):6092-6097
pubmed: 28533409
Genes Dev. 2011 May 15;25(10):1010-22
pubmed: 21576262
Nature. 2001 Nov 8;414(6860):221-5
pubmed: 11700561
Nat Rev Immunol. 2013 Feb;13(2):118-32
pubmed: 23348416
Annu Rev Immunol. 2006;24:541-70
pubmed: 16551259
Cell Rep. 2015 Sep 29;12(12):2086-98
pubmed: 26365193
Cell. 2006 Apr 21;125(2):315-26
pubmed: 16630819
Immunity. 2013 Aug 22;39(2):229-44
pubmed: 23973221
J Clin Oncol. 2012 Jul 10;30(20):2483-91
pubmed: 22564988
Trends Genet. 2018 Dec;34(12):954-971
pubmed: 30217559
Nat Rev Immunol. 2011 Apr;11(4):251-63
pubmed: 21394103
Nat Commun. 2015 May 11;6:7084
pubmed: 25959683
Front Immunol. 2017 Sep 04;8:1076
pubmed: 28928744
Cell Stem Cell. 2014 Jun 5;14(6):710-9
pubmed: 24905162
J Exp Med. 2016 Mar 7;213(3):303-12
pubmed: 26903242
Mol Cell Biol. 2005 Mar;25(5):1804-20
pubmed: 15713636
Curr Biol. 2002 Oct 15;12(20):1748-55
pubmed: 12401169
Trends Genet. 2012 Apr;28(4):164-74
pubmed: 22386917
Nat Immunol. 2002 May;3(5):463-8
pubmed: 11967540
Cancer Cell. 2013 Oct 14;24(4):528-41
pubmed: 24135283
J Immunol. 2014 Feb 1;192(3):1064-70
pubmed: 24353267
J Immunol. 2001 Mar 1;166(5):3315-23
pubmed: 11207287
J Exp Med. 2013 Nov 18;210(12):2495-502
pubmed: 24145512
Immunity. 2011 Sep 23;35(3):413-25
pubmed: 21903424
PLoS Biol. 2013;11(1):e1001475
pubmed: 23382652
Immunity. 2009 Apr 17;30(4):508-20
pubmed: 19345119
J Exp Med. 2009 May 11;206(5):1073-87
pubmed: 19414557
Trends Biochem Sci. 2015 Mar;40(3):172-81
pubmed: 25661247
Proc Natl Acad Sci U S A. 1981 Dec;78(12):7497-501
pubmed: 6801653
Bioessays. 2012 Mar;34(3):194-204
pubmed: 22247014
Mol Cell Biol. 2008 Oct;28(19):6123-33
pubmed: 18644860
PLoS One. 2014 Jul 15;9(7):e97754
pubmed: 25025377
J Biol Chem. 2004 Dec 10;279(50):52353-60
pubmed: 15448152
Nature. 2017 Mar 2;543(7643):72-77
pubmed: 28225755
J Clin Invest. 2015 Jun;125(6):2203-10
pubmed: 25938781
Genes Dev. 2014 Apr 15;28(8):812-28
pubmed: 24736841
Annu Rev Immunol. 2008;26:261-92
pubmed: 18370922
J Exp Med. 2009 Aug 3;206(8):1817-30
pubmed: 19596805
Science. 2010 Jul 2;329(5987):78-82
pubmed: 20595612
Blood. 2008 Sep 1;112(5):1673-82
pubmed: 18552207
Nat Struct Mol Biol. 2013 Mar;20(3):274-81
pubmed: 23463312
Nat Rev Genet. 2012 May 29;13(7):484-92
pubmed: 22641018
Mol Immunol. 2015 Aug;66(2):284-9
pubmed: 25899867
Nature. 2010 Jul 8;466(7303):253-7
pubmed: 20613842
Nat Protoc. 2013 Dec;8(12):2449-70
pubmed: 24232248
Science. 2010 Aug 20;329(5994):917-23
pubmed: 20671152
Immunity. 2001 Aug;15(2):187-99
pubmed: 11520455
Nat Immunol. 2013 Jul;14(7):749-55
pubmed: 23708250
Mol Cell Biol. 2015 Feb;35(3):529-43
pubmed: 25403489
Nature. 2015 Jan 15;517(7534):321-6
pubmed: 25592537
Immunity. 2007 Nov;27(5):711-22
pubmed: 17980632
Proc Natl Acad Sci U S A. 1981 Aug;78(8):4907-11
pubmed: 6795624