Pioneer factor Pax7 deploys a stable enhancer repertoire for specification of cell fate

被引：112

作者：

Mayran, Alexandre ^{[1
,2
]}

Khetchoumian, Konstantin ^{[1
]}

Hariri, Fadi ^{[3
]}

Pastinen, Tomi ^{[3
]}

Gauthier, Yves ^{[1
]}

Balsalobre, Aurelio ^{[1
]}

Drouin, Jacques ^{[1
,2
]}

机构：

[1] IRCM, Lab Genet Mol, Montreal, PQ, Canada

[2] McGill Univ, Dept Biochem, Montreal, PQ, Canada

[3] McGill Univ, McGill Genome Innovat Ctr, Montreal, PQ, Canada

来源：

NATURE GENETICS | 2018年 / 50卷 / 02期

基金：

加拿大健康研究院;

关键词：

TRANSCRIPTION FACTORS; REGULATORY ELEMENTS; CHROMATIN; GENOME; BINDING; FOXA1; RECRUITMENT; MACROPHAGE; EXPRESSION; LANDSCAPE;

D O I：

10.1038/s41588-017-0035-2

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Pioneer transcription factors establish new cell-fate competence by triggering chromatin remodeling. However, many features of pioneer action, such as their kinetics and stability, remain poorly defined. Here, we show that Pax7, by opening a unique repertoire of enhancers, is necessary and sufficient for specification of one pituitary lineage. Pax7 binds its targeted enhancers rapidly, but chromatin remodeling and gene activation are slower. Enhancers opened by Pax7 show a loss of DNA methylation and acquire stable epigenetic memory, as evidenced by binding of nonpioneer factors after Pax7 withdrawal. This work shows that transient Pax7 expression is sufficient for stable specification of cell identity.

引用

页码：259 / +

页数：12

共 41 条

[11] CTCF: making the right connections [J].

Ghirlando, Rodolfo ;

Felsenfeld, Gary .

GENES & DEVELOPMENT, 2016, 30 (08) :881-891

[12] Simple Combinations of Lineage-Determining Transcription Factors Prime cis-Regulatory Elements Required for Macrophage and B Cell Identities [J].

Heinz, Sven ;

Benner, Christopher ;

Spann, Nathanael ;

Bertolino, Eric ;

Lin, Yin C. ;

Laslo, Peter ;

Cheng, Jason X. ;

Murre, Cornelis ;

Singh, Harinder ;

Glass, Christopher K. .

MOLECULAR CELL, 2010, 38 (04) :576-589

[13] Carm1 Regulates Pax7 Transcriptional Activity through MLL1/2 Recruitment during Asymmetric Satellite Stem Cell Divisions [J].

Kawabe, Yoh-ichi ;

Wang, Yu Xin ;

McKinnell, Iain W. ;

Bedford, Mark T. ;

Rudnicki, Michael A. .

CELL STEM CELL, 2012, 11 (03) :333-345

[14] TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions [J].

Kim, Daehwan ;

Pertea, Geo ;

Trapnell, Cole ;

Pimentel, Harold ;

Kelley, Ryan ;

Salzberg, Steven L. .

GENOME BIOLOGY, 2013, 14 (04)

[15] Bismark: a flexible aligner and methylation caller for Bisulfite-Seq applications [J].

Krueger, Felix ;

Andrews, Simon R. .

BIOINFORMATICS, 2011, 27 (11) :1571-1572

[16] Location analysis of estrogen receptor α target promoters reveals that FOXA1 defines a domain of the estrogen response [J].

Laganière, J ;

Deblois, G ;

Lefebvre, C ;

Bataille, AR ;

Robert, F ;

Giguère, V .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (33) :11651-11656

[17] A pituitary cell-restricted T box factor, Tpit, activates POMC transcription in cooperation with Pitx homeoproteins [J].

Lamolet, B ;

Pulichino, AM ;

Lamonerie, T ;

Gauthier, Y ;

Brue, T ;

Enjalbert, A ;

Drouin, J .

CELL, 2001, 104 (06) :849-859

[18] Adult Pituitary Cell Maintenance: Lineage-Specific Contribution of Self-Duplication [J].

Langlais, David ;

Couture, Catherine ;

Kmita, Marie ;

Drouin, Jacques .

MOLECULAR ENDOCRINOLOGY, 2013, 27 (07) :1103-1112

[19] The Stat3/GR Interaction Code: Predictive Value of Direct/Indirect DNA Recruitment for Transcription Outcome [J].

Langlais, David ;

Couture, Catherine ;

Balsalobre, Aurelio ;

Drouin, Jacques .

MOLECULAR CELL, 2012, 47 (01) :38-49

[20] Ultrafast and memory-efficient alignment of short DNA sequences to the human genome [J].

Langmead, Ben ;

Trapnell, Cole ;

Pop, Mihai ;

Salzberg, Steven L. .

GENOME BIOLOGY, 2009, 10 (03)

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