Epigenomic Comparison Reveals Activation of "Seed" Enhancers during Transition from Naive to Primed Pluripotency

被引:116
作者
Factor, Daniel C. [1 ]
Corradin, Olivia [1 ]
Zentner, Gabriel E. [1 ]
Saiakhova, Alina [1 ]
Song, Lingyun [5 ]
Chenoweth, Josh G. [4 ]
McKay, Ronald D. [4 ]
Crawford, Gregory E. [5 ]
Scacheri, Peter C. [1 ,2 ]
Tesar, Paul J. [1 ,2 ,3 ]
机构
[1] Case Western Reserve Univ, Sch Med, Dept Genet & Genome Sci, Cleveland, OH 44106 USA
[2] Case Western Reserve Univ, Sch Med, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA
[3] Case Western Reserve Univ, Sch Med, Natl Ctr Regenerat Med, Cleveland, OH 44106 USA
[4] Lieber Inst Brain Dev, Baltimore, MD 21205 USA
[5] Duke Univ, Inst Genome Sci & Policy, Durham, NC 27709 USA
关键词
EPIBLAST STEM-CELLS; SUPER-ENHANCERS; GROUND-STATE; DISTINCT; DERIVATION; SIGNATURES; INDUCTION; PATTERNS; IDENTITY; MEDIATOR;
D O I
10.1016/j.stem.2014.05.005
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Naive mouse embryonic stem cells (mESCs) and primed epiblast stem cells (mEpiSCs) represent successive snapshots of pluripotency during embryogenesis. Using transcriptomic and epigenomic mapping we show that a small fraction of transcripts are differentially expressed between mESCs and mEpiSCs and that these genes show expected changes in chromatin at their promoters and enhancers. Unexpectedly, the cis-regulatory circuitry of genes that are expressed at identical levels between these cell states also differs dramatically. In mESCs, these genes are associated with dominant proximal enhancers and dormant distal enhancers, which we term seed enhancers. In mEpiSCs, the naive-dominant enhancers are lost, and the seed enhancers take up primary transcriptional control. Seed enhancers have increased sequence conservation and show preferential usage in downstream somatic tissues, often expanding into super enhancers. We propose that seed enhancers ensure proper enhancer utilization and transcriptional fidelity as mammalian cells transition from naive pluripotency to a somatic regulatory program.
引用
收藏
页码:854 / 863
页数:10
相关论文
共 44 条
[1]   FORMATION OF GERM-LINE CHIMERAS FROM EMBRYO-DERIVED TERATOCARCINOMA CELL-LINES [J].
BRADLEY, A ;
EVANS, M ;
KAUFMAN, MH ;
ROBERTSON, E .
NATURE, 1984, 309 (5965) :255-256
[2]   Derivation of pluripotent epiblast stem cells from mammalian embryos [J].
Brons, I. Gabrielle M. ;
Smithers, Lucy E. ;
Trotter, Matthew W. B. ;
Rugg-Gunn, Peter ;
Sun, Bowen ;
de Sousa Lopes, Susana M. Chuva ;
Howlett, Sarah K. ;
Clarkson, Amanda ;
Ahrlund-Richter, Lars ;
Pedersen, Roger A. ;
Vallier, Ludovic .
NATURE, 2007, 448 (7150) :191-U7
[3]   Reorganization of Enhancer Patterns in Transition from Naive to Primed Pluripotency [J].
Buecker, Christa ;
Srinivasan, Rajini ;
Wu, Zhixiang ;
Calo, Eliezer ;
Acampora, Dario ;
Faial, Tiago ;
Simeone, Antonio ;
Tan, Minjia ;
Swigut, Tomasz ;
Wysocka, Joanna .
CELL STEM CELL, 2014, 14 (06) :838-853
[4]   Induction of a Human Pluripotent State with Distinct Regulatory Circuitry that Resembles Preimplantation Epiblast [J].
Chan, Yun-Shen ;
Goeke, Jonathan ;
Ng, Jia-Hui ;
Lu, Xinyi ;
Gonzales, Kevin Andrew Uy ;
Tan, Cheng-Peow ;
Tng, Wei-Quan ;
Hong, Zhong-Zhi ;
Lim, Yee-Siang ;
Ng, Huck-Hui .
CELL STEM CELL, 2013, 13 (06) :663-675
[5]  
Chenoweth JG, 2010, METHODS MOL BIOL, V636, P25, DOI 10.1007/978-1-60761-691-7_2
[6]   Epiblast stem cells contribute new insight into pluripotency and gastrulation [J].
Chenoweth, Josh G. ;
McKay, Ronald D. G. ;
Tesar, Paul J. .
DEVELOPMENT GROWTH & DIFFERENTIATION, 2010, 52 (03) :293-301
[7]   Combinatorial effects of multiple enhancer variants in linkage disequilibrium dictate levels of gene expression to confer susceptibility to common traits [J].
Corradin, Olivia ;
Saiakhova, Alina ;
Akhtar-Zaidi, Batool ;
Myeroff, Lois ;
Willis, Joseph ;
Iari, Richard Cowper-Sal ;
Lupien, Mathieu ;
Markowitz, Sanford ;
Scacheri, Peter C. .
GENOME RESEARCH, 2014, 24 (01) :1-13
[8]   Histone H3K27ac separates active from poised enhancers and predicts developmental state [J].
Creyghton, Menno P. ;
Cheng, Albert W. ;
Welstead, G. Grant ;
Kooistra, Tristan ;
Carey, Bryce W. ;
Steine, Eveline J. ;
Hanna, Jacob ;
Lodato, Michael A. ;
Frampton, Garrett M. ;
Sharp, Phillip A. ;
Boyer, Laurie A. ;
Young, Richard A. ;
Jaenisch, Rudolf .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (50) :21931-21936
[9]   ESTABLISHMENT IN CULTURE OF PLURIPOTENTIAL CELLS FROM MOUSE EMBRYOS [J].
EVANS, MJ ;
KAUFMAN, MH .
NATURE, 1981, 292 (5819) :154-156
[10]   Embryonic stem cells expressing both platelet endothelial cell adhesion molecule-1 and stage-specific embryonic antigen-1 differentiate predominantly into epiblast cells in a chimeric embryo [J].
Furusawa, T ;
Ohkoshi, K ;
Honda, C ;
Takahashi, S ;
Tokunaga, T .
BIOLOGY OF REPRODUCTION, 2004, 70 (05) :1452-1457