Inhibition of H3K27me3 Demethylases Promotes Plasmablast Formation.
Journal
ImmunoHorizons
ISSN: 2573-7732
Titre abrégé: Immunohorizons
Pays: United States
ID NLM: 101708159
Informations de publication
Date de publication:
08 12 2021
08 12 2021
Historique:
received:
02
10
2020
accepted:
15
11
2021
entrez:
9
12
2021
pubmed:
10
12
2021
medline:
8
3
2022
Statut:
epublish
Résumé
B cell differentiation into Ab-secreting plasma cells requires transcriptional, metabolic, and epigenetic remodeling. Histone H3 lysine 27 trimethylation (H3K27me3), a histone modification associated with gene silencing, is dynamically regulated during B cell differentiation. Although several studies have focused on mechanisms involving the gain of this modification in plasmablasts (PB), the role of active demethylation of H3K27me3 by ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX) and Jumonji domain-containing protein 3 (JMDJ3) during B cell differentiation has not been examined. In this study, this process was assessed using a pharmacological inhibitor of UTX and JMJD3, GSK-J4. Treatment of ex vivo stimulated mouse B cells with GSK-J4 led to an increase in PB frequency without affecting the ability of the newly formed PB to secrete Abs. Consistent with the role of UTX and JMJD3 in promoting gene expression, the majority of differentially expressed were downregulated upon GSK-J4 treatment. GSK-J4-treated cells downregulated genes associated with signaling and P53 pathways. Inhibitor treated cells upregulated genes associated with cell cycle and proliferation, which correlated with an increase in actively proliferating cells. Unexpectedly, a majority of the downregulated transcripts corresponded to genes that in the wild-type setting were genes that gain H3K27me3 and downregulated in PB. Together, our results show that UTX and JMDJ3 are required to restrain B cell differentiation and suggest that they function as a rheostat for H3K27me3 to control this process.
Identifiants
pubmed: 34880105
pii: immunohorizons.2000087
doi: 10.4049/immunohorizons.2000087
pmc: PMC10197425
mid: NIHMS1899793
doi:
Substances chimiques
Benzazepines
0
GSK-J4
0
Pyrimidines
0
Histone Demethylases
EC 1.14.11.-
Jumonji Domain-Containing Histone Demethylases
EC 1.14.11.-
Utx protein, mouse
EC 1.14.11.-
Kdm6b protein, mouse
EC 1.5.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
918-930Subventions
Organisme : NIAID NIH HHS
ID : P01 AI125180
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI123733
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008490
Pays : United States
Informations de copyright
Copyright © 2021 The Authors.
Références
Nat Genet. 1995 Jul;10(3):307-12
pubmed: 7670469
Nat Genet. 2009 May;41(5):521-3
pubmed: 19330029
Nat Commun. 2018 Apr 27;9(1):1698
pubmed: 29703886
Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18439-44
pubmed: 18003914
Cell Rep. 2012 Nov 29;2(5):1244-58
pubmed: 23103168
Nat Immunol. 2003 Feb;4(2):124-31
pubmed: 12496962
Nat Immunol. 2016 Oct;17(10):1216-1225
pubmed: 27500631
Cancer Cell. 2013 May 13;23(5):677-92
pubmed: 23680150
Nat Immunol. 2015 Jun;16(6):663-73
pubmed: 25894659
Immunity. 2006 Mar;24(3):283-93
pubmed: 16546097
Dev Cell. 2012 Jan 17;22(1):25-37
pubmed: 22192413
Nat Commun. 2015 Sep 02;6:8152
pubmed: 26328764
Nature. 1993 Dec 16;366(6456):704-7
pubmed: 8259215
J Mol Cell Biol. 2015 Dec;7(6):505-16
pubmed: 25840993
J Immunol. 2012 Sep 1;189(5):2393-403
pubmed: 22851713
Nat Immunol. 2017 Feb;18(2):184-195
pubmed: 27992400
J Cancer Res Clin Oncol. 2018 Jun;144(6):1065-1077
pubmed: 29594337
Nat Rev Immunol. 2009 Mar;9(3):175-84
pubmed: 19240756
Cell Rep. 2017 Oct 17;21(3):628-640
pubmed: 29045832
Hum Mol Genet. 1996 Oct;5(10):1649-55
pubmed: 8894702
Nat Commun. 2018 Jul 13;9(1):2720
pubmed: 30006524
Mol Cell Biol. 2002 Jul;22(13):4771-80
pubmed: 12052884
Science. 2002 Nov 1;298(5595):1039-43
pubmed: 12351676
Nucleic Acids Res. 2014 Jan;42(1):205-23
pubmed: 24078252
Oncotarget. 2017 Jul 10;8(39):65548-65565
pubmed: 29029452
Cytokine. 2012 Jul;59(1):10-7
pubmed: 22507380
Nat Immunol. 2016 Mar;17(3):331-43
pubmed: 26779602
Nat Rev Genet. 2006 Sep;7(9):715-27
pubmed: 16983801
J Hematol Oncol. 2020 Jul 28;13(1):104
pubmed: 32723346
Nature. 2007 Oct 11;449(7163):689-94
pubmed: 17851529
Trends Immunol. 2018 Jan;39(1):19-27
pubmed: 28919256
J Biol Chem. 1997 Oct 17;272(42):26780-6
pubmed: 9334265
Genomics. 1996 Apr 1;33(1):121-3
pubmed: 8617495
Int Immunol. 2008 Mar;20(3):453-60
pubmed: 18256039
Oncogene. 2008 Dec;27 Suppl 1:S114-27
pubmed: 19641497
Nat Rev Immunol. 2015 Mar;15(3):160-71
pubmed: 25698678
Nature. 2014 Oct 2;514(7520):E1-2
pubmed: 25279926
FASEB J. 2019 Apr;33(4):5268-5286
pubmed: 30668141
Cancer Cell. 2016 Aug 8;30(2):197-213
pubmed: 27505670
Immunol Res. 2016 Apr;64(2):345-59
pubmed: 26411453
Immunity. 2017 May 16;46(5):743-755
pubmed: 28514675
Nature. 2004 Jun 3;429(6991):566-71
pubmed: 15152264
Nat Med. 2015 Oct;21(10):1190-8
pubmed: 26366712
Cell. 2002 Oct 18;111(2):197-208
pubmed: 12408864
J Immunol. 2019 Feb 15;202(4):1088-1098
pubmed: 30626691
Genes Dev. 2002 Nov 15;16(22):2893-905
pubmed: 12435631
Nature. 2012 Aug 16;488(7411):404-8
pubmed: 22842901
Nat Genet. 2018 Jun;50(6):883-894
pubmed: 29736013
Immunol Rev. 2019 Mar;288(1):75-84
pubmed: 30874352
Nature. 1999 Oct 7;401(6753):556-62
pubmed: 10524622
Nat Commun. 2014 Dec 22;5:5780
pubmed: 25531312
Cell. 2002 Oct 18;111(2):185-96
pubmed: 12408863
Mol Cell Biol. 2020 Sep 28;40(20):
pubmed: 32817139
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Nat Immunol. 2010 Oct;11(10):936-44
pubmed: 20729857
Semin Immunol. 2008 Feb;20(1):49-58
pubmed: 18222702
Biochem Biophys Res Commun. 1992 Dec 15;189(2):749-58
pubmed: 1339280
Cell Biosci. 2017 May 17;7:25
pubmed: 28529687
Nature. 1997 May 15;387(6630):299-303
pubmed: 9153396
Genes Dev. 2011 Nov 1;25(21):2266-77
pubmed: 22002947
Biochem Soc Trans. 2003 Dec;31(Pt 6):1143-51
pubmed: 14641014
Immunity. 2013 May 23;38(5):918-29
pubmed: 23684984
Nat Commun. 2017 Nov 10;8(1):1426
pubmed: 29127283
Mol Cell Biol. 2007 Mar;27(5):1889-903
pubmed: 17178841
Biochemistry. 2018 Feb 6;57(5):585-592
pubmed: 29220567
Mol Cell. 2017 Jul 20;67(2):308-321.e6
pubmed: 28732206
Pancreas. 2012 Jan;41(1):10-4
pubmed: 22129529
Clin Cancer Res. 2016 Dec 1;22(23):5783-5794
pubmed: 27235425
Trends Immunol. 2013 Sep;34(9):460-70
pubmed: 23643790
Nucleic Acids Res. 2016 May 5;44(8):3659-74
pubmed: 26762983
J Mol Biol. 2004 May 21;339(1):17-29
pubmed: 15123417
Oncogene. 2011 Apr 28;30(17):2037-43
pubmed: 21242977
Immunity. 2006 Aug;25(2):225-36
pubmed: 16919487
Nat Immunol. 2011 Oct 30;12(12):1212-20
pubmed: 22037603
J Exp Med. 2016 May 30;213(6):1095-111
pubmed: 27217539
Signal Transduct Target Ther. 2019 Dec 17;4:62
pubmed: 31871779
Int J Cancer. 2016 Feb 15;138(4):809-17
pubmed: 25868605
Immunity. 2003 Oct;19(4):607-20
pubmed: 14563324
Oncotarget. 2016 May 17;7(20):29387-99
pubmed: 27102442
Biochemistry. 2001 Oct 16;40(41):12387-94
pubmed: 11591158
J Clin Invest. 2013 Dec;123(12):5009-22
pubmed: 24200695
J Immunol. 2018 Feb 1;200(3):1039-1052
pubmed: 29288200
J Immunol. 2018 Nov 1;201(9):2799-2811
pubmed: 30232138
J Exp Med. 2004 Oct 18;200(8):967-77
pubmed: 15492122
Proc Natl Acad Sci U S A. 2012 Aug 7;109(32):13004-9
pubmed: 22826230
Mol Cell. 2010 Nov 24;40(4):594-605
pubmed: 21095589
Genome Res. 2015 Oct;25(10):1473-81
pubmed: 26430157
Blood. 2013 Mar 28;121(13):2462-73
pubmed: 23365460
Front Immunol. 2015 Dec 14;6:631
pubmed: 26697022
Haematologica. 2017 Feb;102(2):373-380
pubmed: 27742770
J Biol Chem. 2014 Jun 27;289(26):18302-13
pubmed: 24798337
J Biol Chem. 2007 Jul 13;282(28):20395-406
pubmed: 17500065
PLoS Genet. 2012 Sep;8(9):e1002964
pubmed: 23028370
J Immunol. 1999 Jul 15;163(2):611-7
pubmed: 10395648
J Immunol. 1997 Apr 1;158(7):3197-204
pubmed: 9120274
Nat Immunol. 2019 Jan;20(1):86-96
pubmed: 30538335