Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression.


:Targeted gene regulation on a genome-wide scale is a powerful strategy for interrogating, perturbing, and engineering cellular systems. Here, we develop a method for controlling gene expression based on Cas9, an RNA-guided DNA endonuclease from a type II CRISPR system. We show that a catalytically dead Cas9 lacking endonuclease activity, when coexpressed with a guide RNA, generates a DNA recognition complex that can specifically interfere with transcriptional elongation, RNA polymerase binding, or transcription factor binding. This system, which we call CRISPR interference (CRISPRi), can efficiently repress expression of targeted genes in Escherichia coli, with no detectable off-target effects. CRISPRi can be used to repress multiple target genes simultaneously, and its effects are reversible. We also show evidence that the system can be adapted for gene repression in mammalian cells. This RNA-guided DNA recognition platform provides a simple approach for selectively perturbing gene expression on a genome-wide scale.






Qi LS,Larson MH,Gilbert LA,Doudna JA,Weissman JS,Arkin AP,Lim WA




Has Abstract


2013-02-28 00:00:00
















  • Hematopoiesis: an evolving paradigm for stem cell biology.

    abstract::Establishment and maintenance of the blood system relies on self-renewing hematopoietic stem cells (HSCs) that normally reside in small numbers in the bone marrow niche of adult mammals. This Review describes the developmental origins of HSCs and the molecular mechanisms that regulate lineage-specific differentiation....


    pub_type: 杂志文章


    authors: Orkin SH,Zon LI

    更新日期:2008-02-22 00:00:00

  • Disentangling inborn and acquired immunity in human twins.

    abstract::The human geneticist Archibald Garrod noted in 1931 that, "It is, of necessity, no easy matter to distinguish between immunity which is inborn and that which has been acquired" (The Inborn Factors in Disease). In this issue of Cell, Brodin et al. show that the heritability of blood counts rapidly decreases with age fo...


    pub_type: 评论,杂志文章


    authors: Casanova JL,Abel L

    更新日期:2015-01-15 00:00:00

  • PKC gamma mutant mice exhibit mild deficits in spatial and contextual learning.

    abstract::We are undertaking a genetic approach to investigate the role that synaptic modulation in the mammalian central nervous system plays in learning and memory and to identify relevant molecular components. We have generated mice deficient in the gamma isoform of protein kinase C (PKC gamma), an enzyme that has previously...


    pub_type: 杂志文章


    authors: Abeliovich A,Paylor R,Chen C,Kim JJ,Wehner JM,Tonegawa S

    更新日期:1993-12-31 00:00:00

  • Growth rate-dependent global effects on gene expression in bacteria.

    abstract::Bacterial gene expression depends not only on specific regulatory mechanisms, but also on bacterial growth, because important global parameters such as the abundance of RNA polymerases and ribosomes are all growth-rate dependent. Understanding of these global effects is necessary for a quantitative understanding of ge...


    pub_type: 杂志文章


    authors: Klumpp S,Zhang Z,Hwa T

    更新日期:2009-12-24 00:00:00

  • How the sequence of a gene can tune its translation.

    abstract::Sixty-one codons specify 20 amino acids, offering cells many options for encoding a polypeptide sequence. Two new studies (Cannarrozzi et al., 2010; Tuller et al., 2010) now foster the idea that patterns of codon usage can control ribosome speed, fine-tuning translation to increase the efficiency of protein synthesis....


    pub_type: 评论,杂志文章,评审


    authors: Fredrick K,Ibba M

    更新日期:2010-04-16 00:00:00

  • Polycomb repression under the skin.

    abstract::Polycomb group proteins control a hierarchy of gene expression during the differentiation of stem cells. In this issue, Ezhkova et al. (2009) show that repression mediated by Polycomb proteins controls the timing of differentiation of precursor cells of the epidermal lineage. ...


    pub_type: 评论,杂志文章


    authors: Pirrotta V

    更新日期:2009-03-20 00:00:00

  • The Centrosome Is a Selective Condensate that Nucleates Microtubules by Concentrating Tubulin.

    abstract::Centrosomes are non-membrane-bound compartments that nucleate microtubule arrays. They consist of nanometer-scale centrioles surrounded by a micron-scale, dynamic assembly of protein called the pericentriolar material (PCM). To study how PCM forms a spherical compartment that nucleates microtubules, we reconstituted P...


    pub_type: 杂志文章


    authors: Woodruff JB,Ferreira Gomes B,Widlund PO,Mahamid J,Honigmann A,Hyman AA

    更新日期:2017-06-01 00:00:00

  • Monoclonal antibodies: use to detect developmentally regulated antigens on D. discoideum amebae.

    abstract::We have used monoclonal antibodies to detect developmentally regulated cell surface antigens on D. discoideum amebae. A study of an antigen detected using an antibody produced by a hybridoma line implicates a previously undescribed component in the process of cell aggregation. This antigen (consisting of a doublet of ...


    pub_type: 杂志文章


    authors: Brodie C,Klein C,Swierkosz J

    更新日期:1983-04-01 00:00:00

  • The genetic basis for specific anosmia to isovaleric acid in the mouse.

    abstract::The detection and discrimination of odorants in mammals is thought to be mediated by a family of 100-1000 seven transmembrane domain receptor proteins, although none of these putative olfactory receptors have been shown to bind individual odorants with high affinity. We have used a genetic approach to identify the gen...


    pub_type: 杂志文章


    authors: Griff IC,Reed RR

    更新日期:1995-11-03 00:00:00

  • Regulation of fibronectin biosynthesis by glucocorticoids in human fibrosarcoma cells and normal fibroblasts.

    abstract::When treated with the synthetic glucocorticoid dexamethasone, HT1080 human fibrosarcoma cells show changes in morphology, adhesion, and the extracellular matrix. Dexamethasone treatment results in a tenfold increase in the rate of fibronectin biosynthesis in HT1080 cells and a twofold increase in untransformed, normal...


    pub_type: 杂志文章


    authors: Oliver N,Newby RF,Furcht LT,Bourgeois S

    更新日期:1983-05-01 00:00:00

  • xol-1 acts as an early switch in the C. elegans male/hermaphrodite decision.

    abstract::xol-1 is the earliest-acting gene in the known hierarchy that controls C. elegans sex determination and dosage compensation. We show that the primary sex-determining signal (the X/A ratio) directs the choice of sexual fate by regulating xol-1 transcript levels: high xol-1 expression during gastrulation triggers male d...


    pub_type: 杂志文章


    authors: Rhind NR,Miller LM,Kopczynski JB,Meyer BJ

    更新日期:1995-01-13 00:00:00

  • Planar polarity and tissue morphogenesis.

    abstract::Planar polarity is a global, tissue-level phenomenon that coordinates cell behavior in a two-dimensional plane. The Frizzled/planar cell polarity (PCP) and anterior-posterior (AP) patterning systems for planar polarity operate in a variety of cell types and provide direction to cells with different morphologies and be...


    pub_type: 杂志文章,评审


    authors: Zallen JA

    更新日期:2007-06-15 00:00:00

  • Analysis of Human Sequence Data Reveals Two Pulses of Archaic Denisovan Admixture.

    abstract::Anatomically modern humans interbred with Neanderthals and with a related archaic population known as Denisovans. Genomes of several Neanderthals and one Denisovan have been sequenced, and these reference genomes have been used to detect introgressed genetic material in present-day human genomes. Segments of introgres...


    pub_type: 杂志文章


    authors: Browning SR,Browning BL,Zhou Y,Tucci S,Akey JM

    更新日期:2018-03-22 00:00:00

  • Activation and repression of myogenesis in somatic cell hybrids: evidence for trans-negative regulation of MyoD in primary fibroblasts.

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    pub_type: 杂志文章


    authors: Thayer MJ,Weintraub H

    更新日期:1990-10-05 00:00:00

  • Prediction of plant microRNA targets.

    abstract::We predict regulatory targets for 14 Arabidopsis microRNAs (miRNAs) by identifying mRNAs with near complementarity. Complementary sites within predicted targets are conserved in rice. Of the 49 predicted targets, 34 are members of transcription factor gene families involved in developmental patterning or cell differen...


    pub_type: 杂志文章


    authors: Rhoades MW,Reinhart BJ,Lim LP,Burge CB,Bartel B,Bartel DP

    更新日期:2002-08-23 00:00:00

  • The Drosophila plutonium and pan gu genes regulate entry into S phase at fertilization.

    abstract::Mutations in the Drosophila maternal genes plutonium (plu) and pan gu (png) have the striking phenotype that DNA replication initiates in unfertilized eggs. Fertilized eggs from plu or png mutant mothers also have a mutant phenotype; DNA replication is uncoupled from nuclear division, resulting in giant, polyploid nuc...


    pub_type: 杂志文章


    authors: Shamanski FL,Orr-Weaver TL

    更新日期:1991-09-20 00:00:00

  • The TGF-alpha precursor expressed on the cell surface binds to the EGF receptor on adjacent cells, leading to signal transduction.

    abstract::The 50 amino acid form of TGF-alpha is cleaved from a conserved integral membrane glycoprotein by a protease that, in many tumor cells, appears to be limiting. To test whether the membrane-bound precursor has biological activity in the absence of processing, we introduced amino acid substitutions at the proteolytic cl...


    pub_type: 杂志文章


    authors: Wong ST,Winchell LF,McCune BK,Earp HS,Teixidó J,Massagué J,Herman B,Lee DC

    更新日期:1989-02-10 00:00:00

  • Histone deimination antagonizes arginine methylation.

    abstract::Methylation of arginine residues within histone H3 has been linked to active transcription. This modification appears on the estrogen-regulated pS2 promoter when the CARM1 methyltransferase is recruited during transcriptional activation. Here we describe a process, deimination, that converts histone arginine to citrul...


    pub_type: 杂志文章


    authors: Cuthbert GL,Daujat S,Snowden AW,Erdjument-Bromage H,Hagiwara T,Yamada M,Schneider R,Gregory PD,Tempst P,Bannister AJ,Kouzarides T

    更新日期:2004-09-03 00:00:00

  • Rewiring the specificity of two-component signal transduction systems.

    abstract::Two-component signal transduction systems are the predominant means by which bacteria sense and respond to environmental stimuli. Bacteria often employ tens or hundreds of these paralogous signaling systems, comprised of histidine kinases (HKs) and their cognate response regulators (RRs). Faithful transmission of info...


    pub_type: 杂志文章


    authors: Skerker JM,Perchuk BS,Siryaporn A,Lubin EA,Ashenberg O,Goulian M,Laub MT

    更新日期:2008-06-13 00:00:00

  • Topology and regulation of the human eIF4A/4G/4H helicase complex in translation initiation.

    abstract::The RNA helicase eIF4A plays a key role in unwinding of mRNA and scanning during translation initiation. Free eIF4A is a poor helicase and requires the accessory proteins eIF4G and eIF4H. However, the structure of the helicase complex and the mechanisms of stimulation of eIF4A activity have remained elusive. Here we r...


    pub_type: 杂志文章


    authors: Marintchev A,Edmonds KA,Marintcheva B,Hendrickson E,Oberer M,Suzuki C,Herdy B,Sonenberg N,Wagner G

    更新日期:2009-02-06 00:00:00

  • Gene Essentiality Profiling Reveals Gene Networks and Synthetic Lethal Interactions with Oncogenic Ras.

    abstract::The genetic dependencies of human cancers widely vary. Here, we catalog this heterogeneity and use it to identify functional gene interactions and genotype-dependent liabilities in cancer. By using genome-wide CRISPR-based screens, we generate a gene essentiality dataset across 14 human acute myeloid leukemia (AML) ce...


    pub_type: 杂志文章


    authors: Wang T,Yu H,Hughes NW,Liu B,Kendirli A,Klein K,Chen WW,Lander ES,Sabatini DM

    更新日期:2017-02-23 00:00:00

  • Wiskott-Aldrich syndrome protein, a novel effector for the GTPase CDC42Hs, is implicated in actin polymerization.

    abstract::The Rho family of GTPases control diverse biological processes, including cell morphology and mitogenesis. We have identified WASP, the protein that is defective in Wiskott-Aldrich syndrome (WAS), as a novel effector for CDC42Hs, but not for the other Rho family members, Rac and Rho. This interaction is dependent on t...


    pub_type: 杂志文章


    authors: Symons M,Derry JM,Karlak B,Jiang S,Lemahieu V,Mccormick F,Francke U,Abo A

    更新日期:1996-03-08 00:00:00

  • The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells.

    abstract::CD4 T cells potentiate the inflammatory or humoral immune response through the action of Th1 and Th2 cells, respectively. The molecular basis of the differentiation of these cells from naive T cell precursors is, however, unclear. We found that GATA-3 was selectively expressed in Th2 cells. GATA-3 is expressed at a hi...


    pub_type: 杂志文章


    authors: Zheng W,Flavell RA

    更新日期:1997-05-16 00:00:00

  • Alternative RNA splicing of the murine alpha A-crystallin gene: protein-coding information within an intron.

    abstract::The eye lens contains a structural protein (alpha-crystallin), composed of two homologous primary gene products, alpha A2 and alpha B2. In certain rodents, there is another minor alpha-crystallin polypeptide, alpha Ains, which is identical to alpha A2 except for a 22 amino acid insert between residues 63 and 64 of the...


    pub_type: 杂志文章


    authors: King CR,Piatigorsky J

    更新日期:1983-03-01 00:00:00

  • Genetic isolation of ADA2: a potential transcriptional adaptor required for function of certain acidic activation domains.

    abstract::We have devised a genetic strategy to isolate the target of acidic activation domains of transcriptional activators based on toxicity in yeast cells of the chimeric activator, GAL4-VP16. Toxicity required the integrity of both the VP16 acidic activation domain and the GAL4 DNA-binding domain, suggesting that inhibitio...


    pub_type: 杂志文章


    authors: Berger SL,Piña B,Silverman N,Marcus GA,Agapite J,Regier JL,Triezenberg SJ,Guarente L

    更新日期:1992-07-24 00:00:00

  • The isolation and nucleotide sequence of a cDNA encoding the T cell surface protein T4: a new member of the immunoglobulin gene family.

    abstract::The surface glycoproteins T4 and T8 define different functional subsets of T lymphocytes and may act as recognition molecules mediating appropriate interactions between the T cell and its target. Previously we employed gene transfer and subtractive hybridization to isolate a T8 cDNA; now we have isolated and sequenced...


    pub_type: 杂志文章


    authors: Maddon PJ,Littman DR,Godfrey M,Maddon DE,Chess L,Axel R

    更新日期:1985-08-01 00:00:00

  • Movement: How the Brain Communicates with the World.

    abstract::Voluntary movement is a result of signals transmitted through a communication channel that links the internal world in our minds to the physical world around us. Intention can be considered the desire to effect change on our environment, and this is contained in the signals from the brain, passed through the nervous s...


    pub_type: 杂志文章,评审


    authors: Schwartz AB

    更新日期:2016-03-10 00:00:00

  • Role of the Xist gene in X chromosome choosing.

    abstract::In female mammals a "random choice" mechanism decides which of the two X chromosomes will be inactivated. It has been postulated that Xist is crucial for heterochromatinization and thus functions downstream of the choice mechanism. Here we report that females heterozygous for an internal deletion in the Xist gene, whi...


    pub_type: 杂志文章


    authors: Marahrens Y,Loring J,Jaenisch R

    更新日期:1998-03-06 00:00:00

  • Communication by touch: role of cellular extensions in complex animals.

    abstract::Neurons make networks of intercellular connections. Many other cells also send out long cellular extensions and "touch" other cells far away. The extensions are intriguing, but what do they do? Possible rationales for this cell behavior include: (1) forming precise binary connections with the possibility of forming mo...


    pub_type: 杂志文章,评审


    authors: Rørth P

    更新日期:2003-03-07 00:00:00

  • The evi5 oncogene regulates cyclin accumulation by stabilizing the anaphase-promoting complex inhibitor emi1.

    abstract::The anaphase-promoting complex/cyclosome (APC/C) inhibitor Emi1 controls progression to S phase and mitosis by stabilizing key APC/C ubiquitination substrates, including cyclin A. Examining Emi1 binding proteins, we identified the Evi5 oncogene as a regulator of Emi1 accumulation. Evi5 antagonizes SCF(betaTrCP)-depend...


    pub_type: 杂志文章


    authors: Eldridge AG,Loktev AV,Hansen DV,Verschuren EW,Reimann JD,Jackson PK

    更新日期:2006-01-27 00:00:00