Pioneer and nonpioneer factor cooperation drives lineage specific chromatin opening.
Animals
Cell Differentiation
/ genetics
Cell Line, Tumor
Corticotrophs
/ physiology
Enhancer Elements, Genetic
Gene Expression Profiling
Gene Expression Regulation, Developmental
Heterochromatin
/ metabolism
Homeodomain Proteins
/ genetics
Male
Melanotrophs
/ physiology
Mice, Knockout
PAX7 Transcription Factor
/ genetics
Protein Binding
/ genetics
Sequence Analysis, RNA
Single-Cell Analysis
T-Box Domain Proteins
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
23 08 2019
23 08 2019
Historique:
received:
15
01
2019
accepted:
30
07
2019
entrez:
25
8
2019
pubmed:
25
8
2019
medline:
27
12
2019
Statut:
epublish
Résumé
Pioneer transcription factors are characterized by having the unique property of enabling the opening of closed chromatin sites, for implementation of cell fates. We previously found that the pioneer Pax7 specifies melanotrope cells through deployment of an enhancer repertoire, which allows binding of Tpit, a nonpioneer factor that determines the related lineages of melanotropes and corticotropes. Here, we investigate the relation between these two factors in the pioneer mechanism. Cell-specific gene expression and chromatin landscapes are defined by scRNAseq and chromatin accessibility profiling. We find that in vivo deployment of the melanotrope enhancer repertoire and chromatin opening requires both Pax7 and Tpit. In cells, binding of heterochromatin targets by Pax7 is independent of Tpit but Pax7-dependent chromatin opening requires Tpit. The present work shows that pioneer core properties are limited to the ability to recognize heterochromatin targets and facilitate nonpioneer binding. Chromatin opening per se may be provided through cooperation with nonpioneer factors.
Identifiants
pubmed: 31444346
doi: 10.1038/s41467-019-11791-9
pii: 10.1038/s41467-019-11791-9
pmc: PMC6707328
doi:
Substances chimiques
Heterochromatin
0
Homeodomain Proteins
0
PAX7 Transcription Factor
0
Pax7 protein, mouse
0
T-Box Domain Proteins
0
Tbx19 protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3807Subventions
Organisme : Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada)
ID : FDN-154297
Pays : International
Références
Nature. 2007 Jul 19;448(7151):313-7
pubmed: 17554338
Nat Commun. 2019 Aug 23;10(1):3807
pubmed: 31444346
Nat Genet. 2011 Jan;43(1):27-33
pubmed: 21151129
Genes Dev. 2003 Mar 15;17(6):738-47
pubmed: 12651892
Mol Cell Biol. 1997 Nov;17(11):6673-82
pubmed: 9343431
Genome Biol. 2008;9(9):R137
pubmed: 18798982
Mol Cell Biol. 2009 Apr;29(7):1895-908
pubmed: 19139274
Mol Cell Biol. 2000 Jul;20(13):4826-37
pubmed: 10848608
Nat Genet. 2018 Feb;50(2):259-269
pubmed: 29358650
Bioinformatics. 2009 Aug 15;25(16):2078-9
pubmed: 19505943
Nature. 2005 Jun 16;435(7044):944-7
pubmed: 15959514
EMBO J. 2016 Jan 4;35(1):24-45
pubmed: 26516211
Genome Biol. 2009;10(3):R25
pubmed: 19261174
Mech Dev. 1998 Nov;78(1-2):171-8
pubmed: 9858722
Genes Dev. 2006 Oct 15;20(20):2871-86
pubmed: 17043312
Mol Endocrinol. 2008 Jul;22(7):1647-57
pubmed: 18388149
Nat Genet. 2018 Feb;50(2):250-258
pubmed: 29358654
Cell. 2001 Mar 23;104(6):849-59
pubmed: 11290323
Mol Cell. 2002 Feb;9(2):279-89
pubmed: 11864602
Proc Natl Acad Sci U S A. 2005 Aug 16;102(33):11651-6
pubmed: 16087863
Proc Natl Acad Sci U S A. 2011 Jul 26;108(30):12515-20
pubmed: 21746936
Cell. 2016 Apr 21;165(3):593-605
pubmed: 27062924
Cell. 2012 Nov 21;151(5):994-1004
pubmed: 23159369
Nucleic Acids Res. 2015 Jul 1;43(W1):W566-70
pubmed: 25969447
Cell Rep. 2017 Sep 26;20(13):3236-3247
pubmed: 28954238
Nat Methods. 2013 Dec;10(12):1213-8
pubmed: 24097267
Mol Endocrinol. 2004 Apr;18(4):995-1003
pubmed: 14726486
EMBO J. 1998 Jan 2;17(1):244-54
pubmed: 9427758
Genome Biol. 2016 Feb 17;17:29
pubmed: 26887813
Mol Cell. 2010 May 28;38(4):576-89
pubmed: 20513432
Nat Genet. 2018 Jul;50(7):1011-1020
pubmed: 29867222
Genes Dev. 2012 Oct 15;26(20):2299-310
pubmed: 23070814
Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):2907-12
pubmed: 18287078
Proc Natl Acad Sci U S A. 2011 Oct 11;108(41):17016-21
pubmed: 21969581
Cell. 2017 Jan 26;168(3):442-459.e20
pubmed: 28111071
Cell. 2017 Oct 19;171(3):557-572.e24
pubmed: 29053968
Mol Cell. 2012 Jul 13;47(1):38-49
pubmed: 22633955
Brief Bioinform. 2013 Mar;14(2):178-92
pubmed: 22517427
Nat Struct Mol Biol. 2016 Apr;23(4):349-57
pubmed: 26926434
Cell. 2015 Apr 23;161(3):555-568
pubmed: 25892221