Abstract:
: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.
journal_name
Celljournal_title
Cellauthors
Qi LS,Larson MH,Gilbert LA,Doudna JA,Weissman JS,Arkin AP,Lim WAdoi
10.1016/j.cell.2013.02.022subject
Has Abstractpub_date
2013-02-28 00:00:00pages
1173-83issue
5eissn
0092-8674issn
1097-4172pii
S0092-8674(13)00211-0journal_volume
152pub_type
杂志文章相关文献
CELL文献大全abstract::The tumor microenvironment is known to play an important role in tumorigenesis. In this issue, Yang et al. (2008) demonstrate that mast cells heterozygous for the Nf1 gene promote the growth of neurofibromas in a mouse model of neurofibromatosis and that genetic and pharmacological inhibition of these cells is suffici...
journal_title:Cell
pub_type: 评论,杂志文章
doi:10.1016/j.cell.2008.10.009
更新日期:2008-10-31 00:00:00
abstract::Advances in genomic technology have produced an explosion of new information about the genetic basis for human disease, fueling extraordinarily high expectations for improved treatments. This perspective will take brief stock of what genetics/genomics have brought to clinical practice to date and what we might expect ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2011.09.013
更新日期:2011-09-30 00:00:00
abstract::Misfolded proteins accumulating in several neurodegenerative diseases (including Alzheimer, Parkinson, and Huntington diseases) can cause aggregation of their native counterparts through a mechanism similar to the infectious prion protein's induction of a pathogenic conformation onto its cellular isoform. Evidence for...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2011.10.011
更新日期:2011-10-28 00:00:00
abstract::The general transcription factor TFIID is a multiprotein complex containing the TATA-binding protein and several associated factors (TAFs), some of which may function as coactivators that are essential for activated, but not basal, transcription. Here we describe the isolation and characterization of the first gene en...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(93)90664-c
更新日期:1993-01-29 00:00:00
abstract::The complete sequence of a hemagglutinin (HA) gene of a recent human influenza A strain, A/Victoria/3/75, is 1768 nucleotides long and contains the information for 567 amino acids. It codes for a signal peptide of 16 amino acids, the HA1 chain of the mature hemagglutinin of 329 amino acids, a connecting region between...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(80)80045-6
更新日期:1980-03-01 00:00:00
abstract::Inositol phosphates are well-known signaling molecules, whereas the inositol pyrophosphates, such as diphosphoinositol pentakisphosphate (InsP7/IP7) and bis-diphosphoinositol tetrakisphosphate (InsP8/IP8), are less well characterized. We demonstrate physiologic regulation of Dictyostelium chemotaxis by InsP7 mediated ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(03)00640-8
更新日期:2003-09-05 00:00:00
abstract::Reversible protein phosphorylation is a signaling mechanism involved in all cellular processes. To create a systems view of the signaling apparatus in budding yeast, we generated an epistatic miniarray profile (E-MAP) comprised of 100,000 pairwise, quantitative genetic interactions, including virtually all protein and...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2008.12.039
更新日期:2009-03-06 00:00:00
abstract::Clinical trials are key to translating scientific advances into progress in cancer research and care. Confronted by developments in basic science, the landscape of clinical cancer research is rapidly evolving. Here, we review recent changes in clinical trials' design and conduct, and we forecast future directions towa...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2017.01.027
更新日期:2017-02-09 00:00:00
abstract::We report here the identification of thyroid hormone response elements (TREs) that consist of a direct repeat, not a palindrome, of the half-sites. Unlike palindromic TREs, direct repeat TREs do not confer a retinoic acid response. The tandem TRE can be converted into a retinoic acid response element by increasing the...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(91)90020-y
更新日期:1991-06-28 00:00:00
abstract::Malignancy can be suppressed by the immune system in a process termed immunosurveillance. However, to what extent immunosurveillance occurs in spontaneous cancers and the composition of participating cell types remains obscure. Here, we show that cell transformation triggers a tissue-resident lymphocyte response in on...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2016.01.002
更新日期:2016-01-28 00:00:00
abstract::One of the important events in synapse formation is the accumulation of neurotransmitter receptors beneath the presynaptic nerve terminal. Agrin is a component of the synaptic basal lamina that induces the clustering of acetylcholine receptors when bath-applied to muscle fibers in culture. When a cDNA encoding a putat...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(91)90364-5
更新日期:1991-11-29 00:00:00
abstract::Behavioral expression of food-associated memory in fruit flies is constrained by satiety and promoted by hunger, suggesting an influence of motivational state. Here, we identify a neural mechanism that integrates the internal state of hunger and appetitive memory. We show that stimulation of neurons that express neuro...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2009.08.035
更新日期:2009-10-16 00:00:00
abstract::Chronic viral infections represent a major burden to human health, and modulation of the immune system is emerging as a novel approach to fighting such infections. Pellegrini et al. (2011) demonstrate that treatment with the cytokine IL-7 may reinvigorate the immune response to persistent infection by targeting immuno...
journal_title:Cell
pub_type: 评论,杂志文章
doi:10.1016/j.cell.2011.01.038
更新日期:2011-02-18 00:00:00
abstract::Uracil-DNA glycosylase inhibitor (Ugi) is a B. subtilis bacteriophage protein that protects the uracil-containing phage DNA by irreversibly inhibiting the key DNA repair enzyme uracil-DNA glycosylase (UDG). The 1.9 A crystal structure of Ugi complexed to human UDG reveals that the Ugi structure, consisting of a twiste...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(95)90467-0
更新日期:1995-09-08 00:00:00
abstract::Recently, a Drosophila gene has been identified, extradenticle, whose product modulates the morphological consequences of homeotic selector genes. We show here that extradenticle protein raises the DNA binding specificity of Ultrabithorax and abdominal-A but not that of Abdominal-B. We further show that extradenticle ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(94)90526-6
更新日期:1994-08-26 00:00:00
abstract::The accurate timing and execution of organelle biogenesis is crucial for cell physiology. Centriole biogenesis is regulated by Polo-like kinase 4 (Plk4) and initiates in S-phase when a daughter centriole grows from the side of a pre-existing mother. Here, we show that a Plk4 oscillation at the base of the growing cent...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2020.05.018
更新日期:2020-06-25 00:00:00
abstract::The gut epithelium self-renews every several days, providing an important innate defense system that limits bacterial colonization. Nevertheless, many bacterial pathogens, including Shigella, efficiently colonize the intestinal epithelium. Here, we show that the Shigella effector IpaB, when delivered into epithelial c...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2007.06.043
更新日期:2007-08-24 00:00:00
abstract::Ca(2+) binding to synaptotagmin 1 triggers fast exocytosis of synaptic vesicles that have been primed for release by SNARE-complex assembly. Besides synaptotagmin 1, fast Ca(2+)-triggered exocytosis requires complexins. Synaptotagmin 1 and complexins both bind to assembled SNARE complexes, but it is unclear how their ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2006.08.030
更新日期:2006-09-22 00:00:00
abstract::Plants rely heavily on environmental cues to control the timing of developmental transitions. We are beginning to better understand what determines the timing of two of these transitions, the switch from juvenile to adult vegetative development and the transition to flowering. In this review, we discuss how RNA silenc...
journal_title:Cell
pub_type: 杂志文章,评审
doi:10.1016/j.cell.2006.05.005
更新日期:2006-05-19 00:00:00
abstract::Cell lines from rhabdomyosarcomas, which are tumors of muscle origin, have been used as models of CD4-independent HIV infection. These cell lines can be induced to differentiate in vitro. We report here that the vpr gene of HIV1 is sufficient for the differentiation of the human rhabdomyosarcoma cell line TE671. Diffe...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(93)90073-y
更新日期:1993-02-26 00:00:00
abstract::Several recent papers show that differences in histone modification and the use of histone variants at the 5' and 3' ends of genes influence the location and kinetics of transcriptional initiation. The ultimate target of most epigenetic mechanisms may be the regulation of nucleosome occupancy, which in turn controls a...
journal_title:Cell
pub_type: 杂志文章,评审
doi:10.1016/j.cell.2005.12.010
更新日期:2005-12-29 00:00:00
abstract::We present a strategy for generating and analyzing comprehensive genetic-interaction maps, termed E-MAPs (epistatic miniarray profiles), comprising quantitative measures of aggravating or alleviating interactions between gene pairs. Crucial to the interpretation of E-MAPs is their high-density nature made possible by ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2005.08.031
更新日期:2005-11-04 00:00:00
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...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(83)90056-9
更新日期:1983-03-01 00:00:00
abstract::Most physiological functions originate with the communication between organs. Mouse genetics has revived this holistic view of physiology through the identification of inter-organ communications that are unanticipated, functionally important, and would have been difficult to uncover otherwise. This Review highlights t...
journal_title:Cell
pub_type: 杂志文章,评审
doi:10.1016/j.cell.2016.02.043
更新日期:2016-03-10 00:00:00
abstract::Null mutant mice for retinoic acid receptor gamma 2 (RAR gamma 2) or all RAR gamma isoforms were generated. RAR gamma 2 mutants appeared normal, whereas RAR gamma mutants exhibited growth deficiency, early lethality, and male sterility due to squamous metaplasia of the seminal vesicles and prostate. These defects were...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(93)90246-m
更新日期:1993-05-21 00:00:00
abstract::Natural killer (NK) cells play a key role in innate immunity by detecting alterations in self and non-self ligands via paired NK cell receptors (NKRs). Despite identification of numerous NKR-ligand interactions, physiological ligands for the prototypical NK1.1 orphan receptor remain elusive. Here, we identify a viral ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2017.03.002
更新日期:2017-03-23 00:00:00
abstract::The global financial crisis has hit biotech companies hard both in the US and Europe as venture capital dries up. Finding new sources of long-term financing for translating research into new therapeutics will be essential for maintaining innovation and new drug development by biotech companies. ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2009.07.026
更新日期:2009-08-07 00:00:00
abstract::The membrane-bound form of immunoglobulin serves as an antigen-specific receptor for B cells mediating signal transduction and antigen presentation. We have developed an assay that reconstitutes both these physiologic responses with respect to the antigen phosphorylcholine. By introducing specific mutations in the hum...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(90)90171-a
更新日期:1990-10-19 00:00:00
abstract::Amid growing recognition that a successful scientific career requires skills beyond scientific acumen, institutions are racing to provide management training for newly minted principal investigators. ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2008.03.008
更新日期:2008-03-21 00:00:00
abstract::Endoplasmic reticulum (ER) membrane contact sites (MCSs) mark positions where endosomes undergo fission for cargo sorting. To define the role of ER at this unique MCS, we targeted a promiscuous biotin ligase to cargo-sorting domains on endosome buds. This strategy identified the ER membrane protein TMCC1, a member of ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2018.08.030
更新日期:2018-09-20 00:00:00