Nascent transcript analysis of glucocorticoid crosstalk with TNF defines primary and cooperative inflammatory repression.
Journal
Genome research
ISSN: 1549-5469
Titre abrégé: Genome Res
Pays: United States
ID NLM: 9518021
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
18
01
2019
accepted:
06
09
2019
pubmed:
15
9
2019
medline:
6
5
2020
entrez:
15
9
2019
Statut:
ppublish
Résumé
The glucocorticoid receptor (NR3C1, also known as GR) binds to specific DNA sequences and directly induces transcription of anti-inflammatory genes that contribute to cytokine repression, frequently in cooperation with NF-kB. Whether inflammatory repression also occurs through local interactions between GR and inflammatory gene regulatory elements has been controversial. Here, using global run-on sequencing (GRO-seq) in human airway epithelial cells, we show that glucocorticoid signaling represses transcription within 10 min. Many repressed regulatory regions reside within "hyper-ChIPable" genomic regions that are subject to dynamic, yet nonspecific, interactions with some antibodies. When this artifact was accounted for, we determined that transcriptional repression does not require local GR occupancy. Instead, widespread transcriptional induction through canonical GR binding sites is associated with reciprocal repression of distal TNF-regulated enhancers through a chromatin-dependent process, as evidenced by chromatin accessibility and motif displacement analysis. Simultaneously, transcriptional induction of key anti-inflammatory effectors is decoupled from primary repression through cooperation between GR and NF-kB at a subset of regulatory regions. Thus, glucocorticoids exert bimodal restraints on inflammation characterized by rapid primary transcriptional repression without local GR occupancy and secondary anti-inflammatory effects resulting from transcriptional cooperation between GR and NF-kB.
Identifiants
pubmed: 31519741
pii: gr.248187.119
doi: 10.1101/gr.248187.119
pmc: PMC6836729
doi:
Substances chimiques
Chromatin
0
NF-kappa B
0
NR3C1 protein, human
0
RNA, Messenger
0
Receptors, Glucocorticoid
0
TNF protein, human
0
Tumor Necrosis Factor-alpha
0
Dexamethasone
7S5I7G3JQL
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1753-1765Subventions
Organisme : NHLBI NIH HHS
ID : F32 HL136197
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL109557
Pays : United States
Organisme : NIH HHS
ID : S10 OD012300
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA046934
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM125871
Pays : United States
Informations de copyright
© 2019 Sasse et al.; Published by Cold Spring Harbor Laboratory Press.
Références
Front Endocrinol (Lausanne). 2015 Nov 09;6:170
pubmed: 26617572
Can Fam Physician. 2017 Apr;63(4):278-285
pubmed: 28404701
Cell Mol Life Sci. 2014 Jan;71(1):143-63
pubmed: 23784308
BMC Pulm Med. 2015 Oct 14;15:122
pubmed: 26466682
Mol Cell Endocrinol. 2013 Nov 5;380(1-2):55-64
pubmed: 23623868
Bioessays. 2016 Jul;38(7):618-26
pubmed: 27273739
Mol Cell. 2015 Apr 2;58(1):21-34
pubmed: 25752574
Genome Res. 2011 Sep;21(9):1404-16
pubmed: 21750107
Bioessays. 1991 Dec;13(12):667-74
pubmed: 1789784
Trends Endocrinol Metab. 2018 Jan;29(1):42-54
pubmed: 29162310
Bioinformatics. 2011 Apr 1;27(7):1017-8
pubmed: 21330290
Mol Syst Biol. 2016 Jan 20;12(1):855
pubmed: 26792871
Adv Exp Med Biol. 2015;872:279-98
pubmed: 26215999
Mol Cell Endocrinol. 2013 Nov 5;380(1-2):41-54
pubmed: 23267834
Curr Opin Pediatr. 2014 Dec;26(6):697-703
pubmed: 25365149
Sci Rep. 2016 Sep 19;6:33510
pubmed: 27641228
Proc Natl Acad Sci U S A. 2013 Nov 12;110(46):18602-7
pubmed: 24173036
J Clin Invest. 2015 Aug 3;125(8):3037-50
pubmed: 26121748
Genome Biol. 2014;15(12):550
pubmed: 25516281
J Mol Biol. 1994 Jun 24;239(5):664-88
pubmed: 8014988
Genome Res. 2018 Sep;28(9):1272-1284
pubmed: 30097539
Am J Respir Cell Mol Biol. 2017 Aug;57(2):226-237
pubmed: 28375666
Mol Endocrinol. 1999 Apr;13(4):604-18
pubmed: 10194766
Methods Mol Biol. 2012;833:63-87
pubmed: 22183588
J Biol Chem. 2003 Jul 25;278(30):28181-92
pubmed: 12732648
Nucleic Acids Res. 2015 Aug 18;43(14):6959-68
pubmed: 26117547
J Biol Chem. 2016 Jun 10;291(24):12673-87
pubmed: 27076634
J Biol Chem. 2014 Mar 21;289(12):8231-9
pubmed: 24500711
Elife. 2018 Feb 09;7:
pubmed: 29424686
Science. 2008 Dec 19;322(5909):1845-8
pubmed: 19056941
PLoS Genet. 2007 Jun;3(6):e94
pubmed: 17559307
Genes Dev. 2014 May 1;28(9):1018-28
pubmed: 24788520
Adv Exp Med Biol. 2017;966:65-92
pubmed: 28639249
Nucleic Acids Res. 2018 Jan 4;46(D1):D794-D801
pubmed: 29126249
Mol Cell. 2008 Mar 14;29(5):611-24
pubmed: 18342607
Proc Natl Acad Sci U S A. 2019 Jul 9;116(28):14191-14199
pubmed: 31227605
Nat Commun. 2015 Jul 17;6:7796
pubmed: 26183376
Cell. 2016 Apr 21;165(3):593-605
pubmed: 27062924
Cell. 2004 Nov 12;119(4):529-42
pubmed: 15537542
Cell. 2011 Aug 19;146(4):544-54
pubmed: 21835447
Bioinformatics. 2016 Oct 1;32(19):3047-8
pubmed: 27312411
Nucleic Acids Res. 2018 Jan 4;46(D1):D252-D259
pubmed: 29140464
Molecules. 2018 May 10;23(5):null
pubmed: 29748466
Elife. 2014 May 27;3:e02200
pubmed: 24867637
Mol Cell. 2013 Jan 10;49(1):158-71
pubmed: 23159735
Arch Bronconeumol. 2011 Apr;47(4):176-83
pubmed: 21454005
Genome Biol. 2008;9(9):R137
pubmed: 18798982
Genome Res. 2015 Jun;25(6):836-44
pubmed: 25957148
Cell. 2011 May 13;145(4):622-34
pubmed: 21549415
Pharmacol Ther. 2012 Apr;134(1):54-67
pubmed: 22212616
Nat Med. 2014 Aug;20(8):919-26
pubmed: 25064128
Immunity. 2017 Aug 15;47(2):298-309.e5
pubmed: 28801231
Eur J Pharmacol. 2006 Mar 8;533(1-3):2-14
pubmed: 16436275
Epigenetics Chromatin. 2014 Nov 20;7(1):33
pubmed: 25473421
Am J Respir Cell Mol Biol. 2019 Feb;60(2):144-157
pubmed: 30156437
Annu Rev Physiol. 2016;78:155-80
pubmed: 26667074
Biomolecules. 2015 Jun 26;5(3):1266-83
pubmed: 26131974
Cell Rep. 2017 Dec 12;21(11):3022-3031
pubmed: 29241532
Nat Biotechnol. 2011 Jan;29(1):24-6
pubmed: 21221095
PLoS One. 2013;8(1):e53936
pubmed: 23349769
Adv Exp Med Biol. 2015;872:59-81
pubmed: 26215990
Genome Res. 2018 Feb 15;:null
pubmed: 29449408
Am J Physiol Lung Cell Mol Physiol. 2016 Aug 1;311(2):L421-32
pubmed: 27371733
Bioinformatics. 2017 Jan 15;33(2):227-234
pubmed: 27663494
Mol Endocrinol. 2014 Sep;28(9):1522-33
pubmed: 25051172
Yeast. 2016 May;33(5):191-200
pubmed: 26860732
Trends Endocrinol Metab. 2017 Jul;28(7):531-540
pubmed: 28495406
Cell. 2018 Oct 4;175(2):598-599
pubmed: 30290144
Nat Struct Mol Biol. 2013 Jan;20(1):53-8
pubmed: 23222642
Nature. 2009 Feb 12;457(7231):854-8
pubmed: 19212405
J Immunol. 2016 Jan 15;196(2):813-822
pubmed: 26663721
Nature. 2011 May 19;473(7347):337-42
pubmed: 21593866
Nat Protoc. 2014 Aug;9(8):1825-47
pubmed: 24992097
Neuroimmunomodulation. 2015;22(1-2):20-32
pubmed: 25227506
Cold Spring Harb Symp Quant Biol. 2015;80:239-48
pubmed: 26432526
Trends Genet. 2016 Apr;32(4):238-249
pubmed: 26962025
J Biol Chem. 2017 Apr 28;292(17):7163-7172
pubmed: 28283576
Bioinformatics. 2010 Mar 15;26(6):841-2
pubmed: 20110278
Science. 1995 Oct 13;270(5234):286-90
pubmed: 7569976
Nucleic Acids Res. 2014 Dec 1;42(21):13051-60
pubmed: 25378309
Mol Cell Biol. 2013 Jun;33(11):2104-15
pubmed: 23508109
Curr Opin Rheumatol. 2000 May;12(3):171-7
pubmed: 10803744
Ann Am Thorac Soc. 2015 Nov;12 Suppl 2:S112-4
pubmed: 26595726