Functional annotation of native enhancers with a Cas9-histone demethylase fusion

被引：490

作者：

Kearns, Nicola A. ^{[1
,2
]}

Pham, Hannah ^{[1
,2
]}

Tabak, Barbara ^{[2
,3
]}

Genga, Ryan M. ^{[1
,2
]}

Silverstein, Noah J. ^{[3
]}

Garber, Manuel ^{[2
,3
]}

Maehr, Rene ^{[1
,2
]}

机构：

[1] Univ Massachusetts, Sch Med, Diabetes Ctr Excellence, Worcester, MA 01605 USA

[2] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA

[3] Univ Massachusetts, Sch Med, Program Bioinformat & Integrat Biol, Worcester, MA 01605 USA

来源：

NATURE METHODS | 2015年 / 12卷 / 05期

基金：

美国国家卫生研究院;

关键词：

GENE-REGULATION; SELF-RENEWAL; STEM-CELLS; TRANSCRIPTION; CHROMATIN; EXPRESSION; DIFFERENTIATION; ACTIVATION; REPRESSION; PROTEINS;

D O I：

10.1038/nmeth.3325

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Understanding of mammalian enhancers is limited by the lack of a technology to rapidly and thoroughly test the cell type-specific function. Here, we use a nuclease-deficient Cas9 (dCas9)-histone demethylase fusion to functionally characterize previously described and new enhancer elements for their roles in the embryonic stem cell state. Further, we distinguish the mechanism of action of dCas9-LSDSD1 at enhancers from previous dCas9-effectors.

引用

页码：401 / +

页数：6

共 32 条

[1] 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

[2]

Buenrostro JD, 2013, NAT METHODS, V10, P1213, DOI [10.1038/NMETH.2688, 10.1038/nmeth.2688]

[3] Hdac6 regulates Tip60-p400 function in stem cells [J].

Chen, Poshen B. ;

Hung, Jui-Hung ;

Hickman, Taylor L. ;

Coles, Andrew H. ;

Carey, James F. ;

Weng, Zhiping ;

Chu, Feixia ;

Fazzio, Thomas G. .

ELIFE, 2013, 2

[4] Multiplexed activation of endogenous genes by CRISPR-on, an RNA-guided transcriptional activator system [J].

Cheng, Albert W. ;

Wang, Haoyi ;

Yang, Hui ;

Shi, Linyu ;

Katz, Yarden ;

Theunissen, Thorold W. ;

Rangarajan, Sudharshan ;

Shivalila, Chikdu S. ;

Dadon, Daniel B. ;

Jaenisch, Rudolf .

CELL RESEARCH, 2013, 23 (10) :1163-1171

[5] Mapping and analysis of chromatin state dynamics in nine human cell types [J].

Ernst, Jason ;

Kheradpour, Pouya ;

Mikkelsen, Tarjei S. ;

Shoresh, Noam ;

Ward, Lucas D. ;

Epstein, Charles B. ;

Zhang, Xiaolan ;

Wang, Li ;

Issner, Robbyn ;

Coyne, Michael ;

Ku, Manching ;

Durham, Timothy ;

Kellis, Manolis ;

Bernstein, Bradley E. .

NATURE, 2011, 473 (7345) :43-U52

[6]

Esvelt KM, 2013, NAT METHODS, V10, P1116, DOI [10.1038/nmeth.2681, 10.1038/NMETH.2681]

[7] Comparison of TALE designer transcription factors and the CRISPR/dCas9 in regulation of gene expression by targeting enhancers [J].

Gao, Xuefei ;

Tsang, Jason C. H. ;

Gaba, Fortis ;

Wu, Donghai ;

Lu, Liming ;

Liu, Pentao .

NUCLEIC ACIDS RESEARCH, 2014, 42 (20)

[8] A High-Throughput Chromatin Immunoprecipitation Approach Reveals Principles of Dynamic Gene Regulation in Mammals [J].

Garber, Manuel ;

Yosef, Nir ;

Goren, Alon ;

Raychowdhury, Raktima ;

Thielke, Anne ;

Guttman, Mitchell ;

Robinson, James ;

Minie, Brian ;

Chevrier, Nicolas ;

Itzhaki, Zohar ;

Blecher-Gonen, Ronnie ;

Bornstein, Chamutal ;

Amann-Zalcenstein, Daniela ;

Weiner, Assaf ;

Friedrich, Dennis ;

Meldrim, James ;

Ram, Oren ;

Cheng, Christine ;

Gnirke, Andreas ;

Fisher, Sheila ;

Friedman, Nir ;

Wong, Bang ;

Bernstein, Bradley E. ;

Nusbaum, Chad ;

Hacohen, Nir ;

Regev, Aviv ;

Amit, Ido .

MOLECULAR CELL, 2012, 47 (05) :810-822

[9] Genome-Scale CRISPR-Mediated Control of Gene Repression and Activation [J].

Gilbert, Luke A. ;

Horlbeck, Max A. ;

Adamson, Britt ;

Villalta, Jacqueline E. ;

Chen, Yuwen ;

Whitehead, Evan H. ;

Guimaraes, Carla ;

Panning, Barbara ;

Ploegh, Hidde L. ;

Bassik, Michael C. ;

Qi, Lei S. ;

Kampmann, Martin ;

Weissman, Jonathan S. .

CELL, 2014, 159 (03) :647-661

[10] CRISPR-Mediated Modular RNA-Guided Regulation of Transcription in Eukaryotes [J].

Gilbert, Luke A. ;

Larson, Matthew H. ;

Morsut, Leonardo ;

Liu, Zairan ;

Brar, Gloria A. ;

Torres, Sandra E. ;

Stern-Ginossar, Noam ;

Brandman, Onn ;

Whitehead, Evan H. ;

Doudna, Jennifer A. ;

Lim, Wendell A. ;

Weissman, Jonathan S. ;

Qi, Lei S. .

CELL, 2013, 154 (02) :442-451

← 1 2 3 4 →