Open Access
Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex
Silvana Konermann,Mark D. Brigham,Alexandro E. Trevino,Julia Joung,Clea Barcena,Patrick D. Hsu,Naomi Habib,Jonathan S. Gootenberg,Hiroshi Nishimasu,Osamu Nureki,Feng Zhang,Omar O. Abudayyeh +11 more
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The article was published on 2016-05-22 and is currently open access. It has received 1792 citations till now. The article focuses on the topics: CRISPR.read more
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Unique features of long non-coding RNA biogenesis and function
Jeffrey J. Quinn,Howard Y. Chang +1 more
TL;DR: This Review describes special events in the lifetimes of lncRNAs — before, during and after transcription — and discusses how these events ultimately shape the unique characteristics and functional roles of lNCRNAs.
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The emerging role of lncRNAs in cancer
TL;DR: The strategies that led to the identification of cancer-related lncRNAs and the methodologies and challenges involving the study of these molecules are discussed, as well as the imminent applications of these findings to the clinic.
Journal ArticleDOI
Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers
Isaac B. Hilton,Anthony D'Ippolito,Christopher M. Vockley,Pratiksha I. Thakore,Gregory E. Crawford,Timothy E. Reddy,Charles A. Gersbach +6 more
TL;DR: A programmable, CRISPR-Cas9-based acetyltransferase consisting of the nuclease-null dCas9 protein fused to the catalytic core of the human acetyl transferase p300 is described, leading to robust transcriptional activation of target genes from promoters and both proximal and distal enhancers.
Crystal Structure of Cas9 in Complex with Guide RNA and Target DNA
Hiroshi Nishimasu,Naoshi Dohmae,Ryuichiro Ishitani,Osamu Nureki,Fei Ran,Patrick D. Hsu,Silvana Konermann,Soraya I. Shehata,Feng Zhang +8 more
TL;DR: The crystal structure of Streptococcus pyogenes Cas9 in complex with sgRNA and its target DNA at 2.5 Å resolution and accompanying functional analyses have revealed the molecular mechanism of RNA-guided DNA targeting by Cas9, paving the way for the rational design of new, versatile genome-editing technologies.
Journal ArticleDOI
Highly efficient Cas9-mediated transcriptional programming
Alejandro Chavez,Jonathan Scheiman,Suhani Vora,Benjamin W. Pruitt,Marcelle Tuttle,Eswar Prasad Ramachandran Iyer,Shuailiang Lin,Samira Kiani,Christopher D. Guzman,Daniel J. Wiegand,Dmitry Ter-Ovanesyan,Jonathan L. Braff,Noah Davidsohn,Benjamin E. Housden,Norbert Perrimon,Ron Weiss,John Aach,James J. Collins,George M. Church +18 more
TL;DR: An improved transcriptional regulator obtained through the rational design of a tripartite activator, VP64-p65-Rta (VPR), fused to nuclease-null Cas9 is described and demonstrated in activating endogenous coding and noncoding genes and stimulating neuronal differentiation of human induced pluripotent stem cells (iPSCs).
References
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EGFR-mediated re-activation of MAPK signaling contributes to insensitivity of BRAF mutant colorectal cancers to RAF inhibition with vemurafenib
Ryan B. Corcoran,Hiromichi Ebi,Alexa B. Turke,Erin M. Coffee,Michiya Nishino,Alexandria P. Cogdill,Ronald D. Brown,Patricia Della Pelle,Dora Dias-Santagata,Kenneth E. Hung,Keith T. Flaherty,Adriano Piris,Jennifer A. Wargo,Jeffrey Settleman,Mari Mino-Kenudson,Jeffrey A. Engelman +15 more
TL;DR: It is found that EGFR-mediated MAPK pathway reactivation leads to resistance to vemurafenib in BRAF-mutant colorectal cancers and that combined RAF and EGFR inhibition can lead to sustainedMAPK pathway suppression and improved efficacy in vitro and in tumor xenografts.
Journal ArticleDOI
Direct Stimulation of the Guanine Nucleotide Exchange Activity of p115 RhoGEF by Gα13
Matthew J. Hart,Xuejun Jiang,Tohru Kozasa,William Roscoe,William D. Singer,Alfred G. Gilman,Paul C. Sternweis,Gideon Bollag +7 more
TL;DR: The GTPase activities of two G protein alpha subunits, Galpha12 and Galpha13, are stimulated by the Rho guanine nucleotide exchange factor p115 RhoGEF, which can directly link heterotrimeric G proteinalpha subunits to regulation of Rho.
Journal ArticleDOI
Orchestrated response: a symphony of transcription factors for gene control.
Bryan Lemon,Robert Tjian +1 more
TL;DR: The question of how gene expression is regulated in complex eukaryotic genomes has re-focused on the molecular machines that have evolved to navigate through chromatin and mediate transcriptional control.
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Genome-Wide RNAi Analysis of Growth and Viability in Drosophila Cells
Michael Boutros,Amy A. Kiger,Susan Armknecht,Susan Armknecht,Kim Kerr,Kim Kerr,Marc Hild,B. Koch,Stefan A. Haas,Renato Paro,Norbert Perrimon,Norbert Perrimon +11 more
TL;DR: A high-throughput RNA-interference screen of 19,470 double-stranded RNAs in cultured cells to characterize the function of nearly all predicted Drosophila genes in cell growth and viability found 438 dsRNAs that identified essential genes, among which 80% lacked mutant alleles.
Optical control of mammalian endogenous transcription and epigenetic states
Silvana Konermann,Silvana Konermann,Mark D. Brigham,Mark D. Brigham,Mark D. Brigham,Alexandro E. Trevino,Alexandro E. Trevino,Patrick D. Hsu,Patrick D. Hsu,Patrick D. Hsu,Matthias Heidenreich,Matthias Heidenreich,Le Cong,Le Cong,Le Cong,Randall Jeffrey Platt,Randall Jeffrey Platt,David A. Scott,David A. Scott,George M. Church,George M. Church,Feng Zhang,Feng Zhang +22 more
TL;DR: Light-inducible transcriptional effectors (LITEs) as discussed by the authors are a two-hybrid system integrating the customizable TALE DNA-binding domain with the light-sensitive cryptochrome 2 protein and its interacting partner CIB1 from Arabidopsis thaliana.