Abstract：
:Gene silencing is instrumental to interrogate gene function and holds promise for therapeutic applications. Here, we repurpose the endogenous retroviruses' silencing machinery of embryonic stem cells to stably silence three highly expressed genes in somatic cells by epigenetics. This was achieved by transiently expressing combinations of engineered transcriptional repressors that bind to and synergize at the target locus to instruct repressive histone marks and de novo DNA methylation, thus ensuring long-term memory of the repressive epigenetic state. Silencing was highly specific, as shown by genome-wide analyses, sharply confined to the targeted locus without spreading to nearby genes, resistant to activation induced by cytokine stimulation, and relieved only by targeted DNA demethylation. We demonstrate the portability of this technology by multiplex gene silencing, adopting different DNA binding platforms and interrogating thousands of genomic loci in different cell types, including primary T lymphocytes. Targeted epigenome editing might have broad application in research and medicine.
journal_name
Celljournal_title
Cellauthors
Amabile A,Migliara A,Capasso P,Biffi M,Cittaro D,Naldini L,Lombardo Adoi
10.1016/j.cell.2016.09.006subject
Has Abstractpub_date
2016-09-22 00:00:00pages
219-232.e14issue
1eissn
0092-8674issn
1097-4172pii
S0092-8674(16)31236-3journal_volume
167pub_type
杂志文章相关文献
CELL文献大全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：:DNA interstrand crosslinks (ICLs) are toxic DNA lesions whose repair occurs in the S phase of metazoans via an unknown mechanism. Here, we describe a cell-free system based on Xenopus egg extracts that supports ICL repair. During DNA replication of a plasmid containing a site-specific ICL, two replication forks conver...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2008.08.030
更新日期：2008-09-19 00:00:00
abstract：:Thrombin stimulates 32Pi incorporation into phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol 4,5-bis-phosphate (PIP2), and phosphatidylinositol (PI), and initiates DNA synthesis in hamster (NIL) fibroblasts at a half-maximal concentration of 125 ng/ml. Neomycin, which binds PIP2 and PIP, inhibits both thro...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(85)90105-9
更新日期：1985-09-01 00:00:00
abstract：:Ribonucleoproteins (RNPs) mediate key cellular functions such as gene expression and its regulation. Whereas most RNP enzymes are stable in composition and harbor preformed active sites, the spliceosome, which removes noncoding introns from precursor messenger RNAs (pre-mRNAs), follows fundamentally different strategi...
journal_title：Cell
pub_type： 杂志文章,评审
doi：10.1016/j.cell.2009.02.009
更新日期：2009-02-20 00:00:00
abstract：:Posttranslational modifications of histones have been strongly correlated with transcriptional regulation. In this issue of Cell, comprehensively examined the nature of arginine methyltransferases and histone modifications in p53-mediated transcription. ...
journal_title：Cell
pub_type： 评论,杂志文章,评审
doi：10.1016/j.cell.2004.05.021
更新日期：2004-06-11 00:00:00
abstract：:Is the Café Scientifique a fashionable by-product of a comfortable age or an indicator of the changing relationship between science and society? ...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2006.07.006
更新日期：2006-07-28 00:00:00
abstract：:Despite an ever-expanding database of sequenced mammalian genomes to be mined for clues, the emergence of the unique human brain remains an evolutionary enigma. In their new study, trawl the human genome and those of other mammals in search of short conserved DNA elements that show extremely rapid evolution only in hu...
journal_title：Cell
pub_type： 杂志文章,评审
doi：10.1016/j.cell.2006.09.007
更新日期：2006-09-22 00:00:00
abstract：:Reprogramming to induced pluripotent stem cells (iPSCs) proceeds in a stepwise manner with reprogramming factor binding, transcription, and chromatin states changing during transitions. Evidence is emerging that epigenetic priming events early in the process may be critical for pluripotency induction later. Chromatin ...
journal_title：Cell
pub_type： 杂志文章,评审
doi：10.1016/j.cell.2013.02.043
更新日期：2013-03-14 00:00:00
abstract：:Post-translational modifications of histone proteins and exchanges of histone variants of chromatin are central to the regulation of nearly all DNA-templated biological processes. However, the degree and variability of chromatin modifications in specific human immune cells remain largely unknown. Here, we employ a hig...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2018.03.079
更新日期：2018-05-31 00:00:00
abstract：:Even a simple sensory stimulus can elicit distinct innate behaviors and sequences. During sensorimotor decisions, competitive interactions among neurons that promote distinct behaviors must ensure the selection and maintenance of one behavior, while suppressing others. The circuit implementation of these competitive i...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2016.09.009
更新日期：2016-10-20 00:00:00
abstract：:The asymmetries of internal organs are consistently oriented along the left-right axis in all vertebrates, and perturbations of left-right orientation lead to significant congenital disease. We propose a model in which a "left-right coordinator" interacts with the Spemann organizer to coordinate the evolutionarily con...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/s0092-8674(00)81144-7
更新日期：1998-04-03 00:00:00
abstract：:Rapid flow of information in the nervous system involves presynaptic vesicle recycling by clathrin-mediated endocytosis, an event triggered by the alpha-adaptin-containing AP2 complex. We identified a Drosophila alpha-adaptin expressed in the garland cells, imaginal discs, and the CNS. Here we show its role in presyna...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/s0092-8674(00)81923-6
更新日期：1997-03-21 00:00:00
abstract：:Sexual reproduction is almost universal in eukaryotic life and involves the fusion of male and female haploid gametes into a diploid cell. The sperm-restricted single-pass transmembrane protein HAP2-GCS1 has been postulated to function in membrane merger. Its presence in the major eukaryotic taxa-animals, plants, and ...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2017.01.024
更新日期：2017-02-23 00:00:00
abstract：:The p53 tumor suppressor gene is commonly altered in human tumors, predominantly through missense mutations that result in accumulation of mutant p53 protein. These mutations may confer dominant-negative or gain-of-function properties to p53. To ascertain the physiological effects of p53 point mutation, the structural...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2004.11.004
更新日期：2004-12-17 00:00:00
abstract：:Of the several families of adhesion receptors involved in leukocyte-endothelial cell interactions, only the selectins have been shown to initiate leukocyte interaction under physiologic shear; indeed, beta 2 (CD18) intergrins responsible for neutrophil arrest are unable to engage without prior selectin-mediated rollin...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(95)90491-3
更新日期：1995-02-10 00:00:00
abstract：:The proportion of BFU-E normally engaged in DNA synthesis is low in adult B6 (C57BL/6) mice of genotype Fv2rr (resistant to Friend erythroleukemia virus), as shown by 3H-thymidine or hydroxyurea "cell suicide" experiments in vivo and vitro. When bone marrow cells from these mice were subjected to a single wash in alph...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(81)90306-8
更新日期：1981-10-01 00:00:00
abstract：:Embryonic inductions appear to be mediated by the concerted action of different inducing factors that modulate one another's activity. Such modulation is likely to reflect interactions between the signal transduction pathways through which the inducing factors act. We tested this idea for the induction of neural tissu...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(89)90099-8
更新日期：1989-08-25 00:00:00
abstract：:The human multidrug resistance P-glycoprotein is an active transporter that pumps cytotoxic drugs out of cells. Expression of P-glycoprotein is also associated with a volume-activated chloride channel. Here we address the relationship between these two functions. Drug transport requires ATP hydrolysis while, in contra...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(92)90263-c
更新日期：1992-10-02 00:00:00
abstract：:The complement system serves an important role in clearance of pathogens, immune complexes, and apoptotic cells present in the circulation. Complement fragments deposited on the particle surface serve as targets for complement receptors present on phagocytic cells. Although Kupffer cells, the liver resident macrophage...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2005.12.039
更新日期：2006-03-10 00:00:00
abstract：:As axons grow past intermediate targets, they change their responsiveness to guidance cues. Local upregulation of receptor expression is involved, but the mechanisms for this are not clear. Here protein synthesis is traced within individual axons by introducing RNAs encoding visualizable reporters. Individual severed ...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/s0092-8674(02)00813-9
更新日期：2002-07-26 00:00:00
abstract：:Activation of the cyclin-dependent kinases to promote cell cycle progression requires their association with cyclins as well as phosphorylation of a threonine (residue 161 in human p34cdc2). This phosphorylation is carried out by CAK, the Cdk-activating kinase. We have purified and cloned CAK from S. cerevisiae. Unlik...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/s0092-8674(00)80129-4
更新日期：1996-08-23 00:00:00
abstract：:Senescence in Podospora anserina has long been shown to be under cytoplasmic control. Comparison of DNAs isolated from young and senescent cultures made it possible to detect the presence, in senescent cultures only, of a specific DNA (SEN-DNA). This DNA consists of repeated sequences arranged in a multimeric set of c...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(80)90126-9
更新日期：1980-08-01 00:00:00
abstract：:The Wee1 kinase phosphorylates and inhibits cyclin-dependent kinase 1 (Cdk1), thereby delaying entry into mitosis until appropriate conditions have been met. An understanding of the mechanisms that regulate Wee1 should provide new insight into how cells make the decision to enter mitosis. We report here that Swe1, the...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2005.05.029
更新日期：2005-08-12 00:00:00
abstract：:Regulatory T cells (Tregs) play a pivotal role in the inhibition of anti-tumor immune responses. Understanding the mechanisms governing Treg homeostasis may therefore be important for development of effective tumor immunotherapy. We have recently demonstrated a key role for the canonical nuclear factor κB (NF-κB) subu...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2017.08.004
更新日期：2017-09-07 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：:In two companion reports, the TRACERx consortium investigates tumor heterogeneity and evolution in early-stage non-small cell lung cancer. The studies highlight the prognostic value of copy-number heterogeneity assessment in tumor biopsies and circulating tumor DNA detection in plasma and suggest that tracking the evo...
journal_title：Cell
pub_type： 评论,杂志文章
doi：10.1016/j.cell.2017.05.001
更新日期：2017-05-18 00:00:00
abstract：:The majority of the mRNA molecules in HeLa cells contain 1-2 residue(s) of m6Ap and one blocked, methylated 5' terminal "cap" structure. The hnRNA, which is longer than mRNA, contains both m6Ap and caps but 4-6 times as many m6Ap residues per chain. In addition, nuclear molecules contain T2 RNA ase-resistant, methyl-l...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(76)90022-2
更新日期：1976-02-01 00:00:00
abstract：:The v-erbB gene product of avian erythroblastosis virus (AEV) has extensive homology with the receptor for epidermal growth factor (EGF). We report here that chicken embryo fibroblasts (CEF) transformed by AEV show enhanced tyrosine phosphorylation of a number of cellular polypeptides, including the 36 kd protein, whi...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(85)90209-0
更新日期：1985-03-01 00:00:00
abstract：:FtsK acts at the bacterial division septum to couple chromosome segregation with cell division. We demonstrate that a truncated FtsK derivative, FtsK(50C), uses ATP hydrolysis to translocate along duplex DNA as a multimer in vitro, consistent with FtsK having an in vivo role in pumping DNA through the closing division...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/s0092-8674(02)00624-4
更新日期：2002-01-25 00:00:00
abstract：:The symmetric core of the nuclear pore complex can be considered schematically as a series of concentric cylinders. A peripheral cylinder coating the pore membrane contains the previously characterized, elongated heptamer that harbors Sec13-Nup145C in its middle section. Strikingly, Sec13-Nup145C crystallizes as a het...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2007.11.038
更新日期：2007-12-28 00:00:00
