Genome-Wide Quantitative Enhancer Activity Maps Identified by STARR-seq

被引：708

作者：

Arnold, Cosmas D. ^{[1
]}

Gerlach, Daniel ^{[1
]}

Stelzer, Christoph ^{[1
]}

Boryn, Lukasz M. ^{[1
]}

Rath, Martina ^{[1
]}

Stark, Alexander ^{[1
]}

机构：

[1] Res Inst Mol Pathol IMP, A-1030 Vienna, Austria

来源：

SCIENCE | 2013年 / 339卷 / 6123期

基金：

奥地利科学基金会; 欧洲研究理事会;

关键词：

OPEN CHROMATIN; GENE; DISSECTION; EXPRESSION;

D O I：

10.1126/science.1232542

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Genomic enhancers are important regulators of gene expression, but their identification is a challenge, and methods depend on indirect measures of activity. We developed a method termed STARR-seq to directly and quantitatively assess enhancer activity for millions of candidates from arbitrary sources of DNA, which enables screens across entire genomes. When applied to the Drosophila genome, STARR-seq identifies thousands of cell type-specific enhancers across a broad continuum of strengths, links differential gene expression to differences in enhancer activity, and creates a genome-wide quantitative enhancer map. This map reveals the highly complex regulation of transcription, with several independent enhancers for both developmental regulators and ubiquitously expressed genes. STARR-seq can be used to identify and quantify enhancer activity in other eukaryotes, including humans.

引用

页码：1074 / 1077

页数：4

共 21 条

[1] The genome sequence of Drosophila melanogaster [J].

Adams, MD ;

Celniker, SE ;

Holt, RA ;

Evans, CA ;

Gocayne, JD ;

Amanatides, PG ;

Scherer, SE ;

Li, PW ;

Hoskins, RA ;

Galle, RF ;

George, RA ;

Lewis, SE ;

Richards, S ;

Ashburner, M ;

Henderson, SN ;

Sutton, GG ;

Wortman, JR ;

Yandell, MD ;

Zhang, Q ;

Chen, LX ;

Brandon, RC ;

Rogers, YHC ;

Blazej, RG ;

Champe, M ;

Pfeiffer, BD ;

Wan, KH ;

Doyle, C ;

Baxter, EG ;

Helt, G ;

Nelson, CR ;

Miklos, GLG ;

Abril, JF ;

Agbayani, A ;

An, HJ ;

Andrews-Pfannkoch, C ;

Baldwin, D ;

Ballew, RM ;

Basu, A ;

Baxendale, J ;

Bayraktaroglu, L ;

Beasley, EM ;

Beeson, KY ;

Benos, PV ;

Berman, BP ;

Bhandari, D ;

Bolshakov, S ;

Borkova, D ;

Botchan, MR ;

Bouck, J ;

Brokstein, P .

SCIENCE, 2000, 287 (5461) :2185-2195

[2] EXPRESSION OF A BETA-GLOBIN GENE IS ENHANCED BY REMOTE SV40 DNA-SEQUENCES [J].

BANERJI, J ;

RUSCONI, S ;

SCHAFFNER, W .

CELL, 1981, 27 (02) :299-308

[3] Tissue-specific analysis of chromatin state identifies temporal signatures of enhancer activity during embryonic development [J].

Bonn, Stefan ;

Zinzen, Robert P. ;

Girardot, Charles ;

Gustafson, E. Hilary ;

Perez-Gonzalez, Alexis ;

Delhomme, Nicolas ;

Ghavi-Helm, Yad ;

Wilczynski, Bartek ;

Riddell, Andrew ;

Furlong, Eileen E. M. .

NATURE GENETICS, 2012, 44 (02) :148-156

[4] Polycomb complexes repress developmental regulators in murine embryonic stem cells [J].

Boyer, LA ;

Plath, K ;

Zeitlinger, J ;

Brambrink, T ;

Medeiros, LA ;

Lee, TI ;

Levine, SS ;

Wernig, M ;

Tajonar, A ;

Ray, MK ;

Bell, GW ;

Otte, AP ;

Vidal, M ;

Gifford, DK ;

Young, RA ;

Jaenisch, R .

NATURE, 2006, 441 (7091) :349-353

[5] High-resolution mapping and characterization of open chromatin across the genome [J].

Boyle, Alan P. ;

Davis, Sean ;

Shulha, Hennady P. ;

Meltzer, Paul ;

Margulies, Elliott H. ;

Weng, Zhiping ;

Furey, Terrence S. ;

Crawford, Gregory E. .

CELL, 2008, 132 (02) :311-322

[6] 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

[7] Phenotypic robustness conferred by apparently redundant transcriptional enhancers [J].

Frankel, Nicolas ;

Davis, Gregory K. ;

Vargas, Diego ;

Wang, Shu ;

Payre, Francois ;

Stern, David L. .

NATURE, 2010, 466 (7305) :490-U8

[8] A map of open chromatin in human pancreatic islets [J].

Gaulton, Kyle J. ;

Nammo, Takao ;

Pasquali, Lorenzo ;

Simon, Jeremy M. ;

Giresi, Paul G. ;

Fogarty, Marie P. ;

Panhuis, Tami M. ;

Mieczkowski, Piotr ;

Secchi, Antonio ;

Bosco, Domenico ;

Berney, Thierry ;

Montanya, Eduard ;

Mohlke, Karen L. ;

Lieb, Jason D. ;

Ferrer, Jorge .

NATURE GENETICS, 2010, 42 (03) :255-U41

[9] Histone modifications at human enhancers reflect global cell-type-specific gene expression [J].

Heintzman, Nathaniel D. ;

Hon, Gary C. ;

Hawkins, R. David ;

Kheradpour, Pouya ;

Stark, Alexander ;

Harp, Lindsey F. ;

Ye, Zhen ;

Lee, Leonard K. ;

Stuart, Rhona K. ;

Ching, Christina W. ;

Ching, Keith A. ;

Antosiewicz-Bourget, Jessica E. ;

Liu, Hui ;

Zhang, Xinmin ;

Green, Roland D. ;

Lobanenkov, Victor V. ;

Stewart, Ron ;

Thomson, James A. ;

Crawford, Gregory E. ;

Kellis, Manolis ;

Ren, Bing .

NATURE, 2009, 459 (7243) :108-112

[10] Genome-wide mapping of in vivo protein-DNA interactions [J].

Johnson, David S. ;

Mortazavi, Ali ;

Myers, Richard M. ;

Wold, Barbara .

SCIENCE, 2007, 316 (5830) :1497-1502

← 1 2 3 →