Targeted DNA oxidation by LSD1-SMAD2/3 primes TGF-β1/ EMT genes for activation or repression.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
18 09 2020
18 09 2020
Historique:
accepted:
03
07
2020
revised:
24
06
2020
received:
17
03
2020
pubmed:
23
7
2020
medline:
29
10
2020
entrez:
23
7
2020
Statut:
ppublish
Résumé
The epithelial-to-mesenchymal transition (EMT) is a complex transcriptional program induced by transforming growth factor β1 (TGF-β1). Histone lysine-specific demethylase 1 (LSD1) has been recognized as a key mediator of EMT in cancer cells, but the precise mechanism that underlies the activation and repression of EMT genes still remains elusive. Here, we characterized the early events induced by TGF-β1 during EMT initiation and establishment. TGF-β1 triggered, 30-90 min post-treatment, a nuclear oxidative wave throughout the genome, documented by confocal microscopy and mass spectrometry, mediated by LSD1. LSD1 was recruited with phosphorylated SMAD2/3 to the promoters of prototypic genes activated and repressed by TGF-β1. After 90 min, phospho-SMAD2/3 downregulation reduced the complex and LSD1 was then recruited with the newly synthesized SNAI1 and repressors, NCoR1 and HDAC3, to the promoters of TGF-β1-repressed genes such as the Wnt soluble inhibitor factor 1 gene (WIF1), a change that induced a late oxidative burst. However, TGF-β1 early (90 min) repression of transcription also required synchronous signaling by reactive oxygen species and the stress-activated kinase c-Jun N-terminal kinase. These data elucidate the early events elicited by TGF-β1 and the priming role of DNA oxidation that marks TGF-β1-induced and -repressed genes involved in the EMT.
Identifiants
pubmed: 32697292
pii: 5874912
doi: 10.1093/nar/gkaa599
pmc: PMC7498341
doi:
Substances chimiques
SMAD2 protein, human
0
Smad2 Protein
0
TGFB1 protein, human
0
Transforming Growth Factor beta1
0
DNA
9007-49-2
Histone Demethylases
EC 1.14.11.-
KDM1A protein, human
EC 1.5.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
8943-8958Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.
Références
Nat Cell Biol. 2009 Aug;11(8):943-50
pubmed: 19597490
Mol Cell. 2012 Aug 24;47(4):622-32
pubmed: 22771116
Biochemistry. 2007 Apr 10;46(14):4408-16
pubmed: 17367163
Redox Biol. 2019 Sep;26:101272
pubmed: 31330481
Nat Commun. 2017 Oct 19;8(1):997
pubmed: 29051480
Chem Biol. 2014 Nov 20;21(11):1433-43
pubmed: 25442375
Am J Physiol Lung Cell Mol Physiol. 2011 Feb;300(2):L295-304
pubmed: 21131394
J Cell Biol. 2003 Jun 9;161(5):933-44
pubmed: 12796479
Oncotarget. 2014 May 15;5(9):2827-38
pubmed: 24811539
Carcinogenesis. 2008 Dec;29(12):2267-78
pubmed: 18791199
Cell Physiol Biochem. 2018;46(5):2103-2113
pubmed: 29723859
Stem Cell Rev Rep. 2016 Jun;12(3):298-304
pubmed: 27059868
Mol Cell. 1998 Mar;1(4):611-7
pubmed: 9660945
Mol Cell Biol. 2004 Mar;24(6):2546-59
pubmed: 14993291
Hypertension. 2008 Feb;51(2):211-7
pubmed: 18086956
Sci Rep. 2019 Mar 8;9(1):3925
pubmed: 30850627
Mol Metab. 2016 Dec 08;6(2):174-184
pubmed: 28180059
Oncogene. 2010 Sep 2;29(35):4896-904
pubmed: 20562920
Proc Natl Acad Sci U S A. 2017 Apr 4;114(14):E2975-E2982
pubmed: 28320972
Mol Cell. 2013 Nov 7;52(3):291-302
pubmed: 24207023
Oncogene. 2005 Dec 1;24(54):8038-50
pubmed: 16170382
Front Cell Neurosci. 2016 Jun 02;10:146
pubmed: 27313511
PLoS One. 2010 Jan 11;5(1):e8570
pubmed: 20084102
ACS Chem Biol. 2017 Apr 21;12(4):1011-1019
pubmed: 28051298
Cancer Lett. 2013 Nov 28;341(1):80-96
pubmed: 23376253
J Clin Invest. 2009 Jun;119(6):1420-8
pubmed: 19487818
Oncotarget. 2017 Aug 2;8(40):68591-68598
pubmed: 28978140
Nat Commun. 2017 Dec 12;8(1):2070
pubmed: 29234012
Nucleic Acids Res. 2019 Jan 10;47(1):221-236
pubmed: 30462294
Genome Biol. 2005;6(8):227
pubmed: 16086857
Nat Rev Mol Cell Biol. 2002 Mar;3(3):155-66
pubmed: 11994736
Nat Rev Cancer. 2006 May;6(5):392-401
pubmed: 16572188
Nat Rev Genet. 2006 Sep;7(9):715-27
pubmed: 16983801
F1000Res. 2017 Nov 16;6:2016
pubmed: 29225781
Br J Pharmacol. 2010 Oct;161(4):885-98
pubmed: 20860666
Cancer Res. 2010 Sep 1;70(17):6945-56
pubmed: 20699369
Science. 2008 Jan 11;319(5860):202-6
pubmed: 18187655
Nucleic Acids Res. 2017 Oct 13;45(18):10350-10368
pubmed: 28977640
Redox Biol. 2015 Dec;6:565-577
pubmed: 26496488
Curr Top Med Chem. 2016;16(19):2179-88
pubmed: 26881714
Free Radic Biol Med. 2012 Oct 1;53(7):1489-99
pubmed: 22728268
Cancer Metastasis Rev. 2012 Jun;31(1-2):195-208
pubmed: 22101652
Antioxid Redox Signal. 2013 Nov 20;19(15):1828-45
pubmed: 23146119
J Am Soc Nephrol. 2005 Mar;16(3):667-75
pubmed: 15677311
Nat Rev Cancer. 2002 Jun;2(6):442-54
pubmed: 12189386
Sci Signal. 2014 Sep 02;7(341):ra84
pubmed: 25185156
Sci Rep. 2017 Apr 04;7:45465
pubmed: 28374803
Genes Dev. 2016 Apr 1;30(7):733-50
pubmed: 27036965
J Biol Chem. 2009 May 29;284(22):15158-72
pubmed: 19329425
Antioxid Redox Signal. 2011 Jun 15;14(12):2361-71
pubmed: 21235356
NPJ Syst Biol Appl. 2018 May 28;4:18
pubmed: 29872541
DNA Repair (Amst). 2007 Mar 1;6(3):317-28
pubmed: 17126083
Clin Cancer Res. 2013 Jan 1;19(1):279-90
pubmed: 23091115
Anticancer Res. 2013 Oct;33(10):4431-8
pubmed: 24123012
Mutat Res. 2009 Jun 18;666(1-2):16-22
pubmed: 19481675
Nucleic Acids Res. 2014;42(17):11040-55
pubmed: 25217584
Mol Cell. 2003 Apr;11(4):915-26
pubmed: 12718878
Sci Signal. 2012 Jul 03;5(231):ra47
pubmed: 22763339
FEBS Lett. 2005 Apr 11;579(10):2203-7
pubmed: 15811342
Sci Signal. 2019 Feb 26;12(570):
pubmed: 30808819
Anal Chem. 2016 Dec 20;88(24):12128-12136
pubmed: 28193047
Nat Commun. 2013;4:2035
pubmed: 23792809