Decoding enhancers using massively parallel reporter assays

被引:176
作者
Inoue, Fumitaka
Ahituv, Nadav [1 ]
机构
[1] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94158 USA
关键词
Enhancer; Massively parallel reporter assays; Transcriptional regulation; TISSUE-SPECIFIC ENHANCERS; REGULATORY ELEMENTS; OPEN CHROMATIN; ACTIVITY MAPS; HUMAN GENOME; IN-VIVO; SYSTEMATIC DISSECTION; PROMOTERS; SEQUENCES; SEQ;
D O I
10.1016/j.ygeno.2015.06.005
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Enhancers control the timing, location and expression levels of their target genes. Nucleotide variation in enhancers has been shown to lead to numerous phenotypes, including human disease. While putative enhancer sequences and nucleotide variation within them can now be detected in a rapid manner using various genomic technologies, the understanding of the functional consequences of these variants still remains largely unknown. Massively parallel reporter assays (MPRAs) can overcome this hurdle by providing the ability to test thousands of sequences and nucleotide variants within them for enhancer activity en masse. Here, we describe this technology and specifically focus on how it is being used to obtain an increased understanding of enhancer regulatory code and grammar. (C) 2015 Elsevier Inc. All rights reserved.
引用
收藏
页码:159 / 164
页数:6
相关论文
共 50 条
[1]  
Ahituv N., 2012, Gene Regulatory Sequences and Human Disease
[2]   Chromatin Position Effects Assayed by Thousands of Reporters Integrated in Parallel [J].
Akhtar, Waseem ;
de Jong, Johann ;
Pindyurin, Alexey V. ;
Pagie, Ludo ;
Meuleman, Wouter ;
de Ridder, Jeroen ;
Berns, Anton ;
Wessels, Lodewyk F. A. ;
van Lohuizen, Maarten ;
van Steensel, Bas .
CELL, 2013, 154 (04) :914-927
[3]   An atlas of active enhancers across human cell types and tissues [J].
Andersson, Robin ;
Gebhard, Claudia ;
Miguel-Escalada, Irene ;
Hoof, Ilka ;
Bornholdt, Jette ;
Boyd, Mette ;
Chen, Yun ;
Zhao, Xiaobei ;
Schmidl, Christian ;
Suzuki, Takahiro ;
Ntini, Evgenia ;
Arner, Erik ;
Valen, Eivind ;
Li, Kang ;
Schwarzfischer, Lucia ;
Glatz, Dagmar ;
Raithel, Johanna ;
Lilje, Berit ;
Rapin, Nicolas ;
Bagger, Frederik Otzen ;
Jorgensen, Mette ;
Andersen, Peter Refsing ;
Bertin, Nicolas ;
Rackham, Owen ;
Burroughs, A. Maxwell ;
Baillie, J. Kenneth ;
Ishizu, Yuri ;
Shimizu, Yuri ;
Furuhata, Erina ;
Maeda, Shiori ;
Negishi, Yutaka ;
Mungall, Christopher J. ;
Meehan, Terrence F. ;
Lassmann, Timo ;
Itoh, Masayoshi ;
Kawaji, Hideya ;
Kondo, Naoto ;
Kawai, Jun ;
Lennartsson, Andreas ;
Daub, Carsten O. ;
Heutink, Peter ;
Hume, David A. ;
Jensen, Torben Heick ;
Suzuki, Harukazu ;
Hayashizaki, Yoshihide ;
Mueller, Ferenc ;
Forrest, Alistair R. R. ;
Carninci, Piero ;
Rehli, Michael ;
Sandelin, Albin .
NATURE, 2014, 507 (7493) :455-+
[4]   Quantitative genome-wide enhancer activity maps for five Drosophila species show functional enhancer conservation and turnover during cis-regulatory evolution [J].
Arnold, Cosmas D. ;
Gerlach, Daniel ;
Spies, Daniel ;
Matts, Jessica A. ;
Sytnikova, Yuliya A. ;
Pagani, Michaela ;
Lau, Nelson C. ;
Stark, Alexander .
NATURE GENETICS, 2014, 46 (07) :685-692
[5]   Genome-Wide Quantitative Enhancer Activity Maps Identified by STARR-seq [J].
Arnold, Cosmas D. ;
Gerlach, Daniel ;
Stelzer, Christoph ;
Boryn, Lukasz M. ;
Rath, Martina ;
Stark, Alexander .
SCIENCE, 2013, 339 (6123) :1074-1077
[6]   Systematic Dissection of Coding Exons at Single Nucleotide Resolution Supports an Additional Role in Cell-Specific Transcriptional Regulation [J].
Birnbaum, Ramon Y. ;
Patwardhan, Rupali P. ;
Kim, Mee J. ;
Findlay, Gregory M. ;
Martin, Beth ;
Zhao, Jingjing ;
Bell, Robert J. A. ;
Smith, Robin P. ;
Ku, Angel A. ;
Shendure, Jay ;
Ahituv, Nadav .
PLOS GENETICS, 2014, 10 (10)
[7]   Coding exons function as tissue-specific enhancers of nearby genes [J].
Birnbaum, Ramon Y. ;
Clowney, E. Josephine ;
Agamy, Orly ;
Kim, Mee J. ;
Zhao, Jingjing ;
Yamanaka, Takayuki ;
Pappalardo, Zachary ;
Clarke, Shoa L. ;
Wenger, Aaron M. ;
Loan Nguyen ;
Gurrieri, Fiorella ;
Everman, David B. ;
Schwartz, Charles E. ;
Birk, Ohad S. ;
Bejerano, Gill ;
Lomvardas, Stavros ;
Ahituv, Nadav .
GENOME RESEARCH, 2012, 22 (06) :1059-1068
[8]   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
[9]  
Buenrostro JD, 2013, NAT METHODS, V10, P1213, DOI [10.1038/nmeth.2688, 10.1038/NMETH.2688]
[10]   Evolution at two levels: On genes and form [J].
Carroll, SB .
PLOS BIOLOGY, 2005, 3 (07) :1159-1166