Abstract:
:Embryonic stem cells (ESCs) repress the expression of exogenous proviruses and endogenous retroviruses (ERVs). Here, we systematically dissected the cellular factors involved in provirus repression in embryonic carcinomas (ECs) and ESCs by a genome-wide siRNA screen. Histone chaperones (Chaf1a/b), sumoylation factors (Sumo2/Ube2i/Sae1/Uba2/Senp6), and chromatin modifiers (Trim28/Eset/Atf7ip) are key determinants that establish provirus silencing. RNA-seq analysis uncovered the roles of Chaf1a/b and sumoylation modifiers in the repression of ERVs. ChIP-seq analysis demonstrates direct recruitment of Chaf1a and Sumo2 to ERVs. Chaf1a reinforces transcriptional repression via its interaction with members of the NuRD complex (Kdm1a, Hdac1/2) and Eset, while Sumo2 orchestrates the provirus repressive function of the canonical Zfp809/Trim28/Eset machinery by sumoylation of Trim28. Our study reports a genome-wide atlas of functional nodes that mediate proviral silencing in ESCs and illuminates the comprehensive, interconnected, and multi-layered genetic and epigenetic mechanisms by which ESCs repress retroviruses within the genome.
journal_name
Celljournal_title
Cellauthors
Yang BX,El Farran CA,Guo HC,Yu T,Fang HT,Wang HF,Schlesinger S,Seah YF,Goh GY,Neo SP,Li Y,Lorincz MC,Tergaonkar V,Lim TM,Chen L,Gunaratne J,Collins JJ,Goff SP,Daley GQ,Li H,Bard FA,Loh YHdoi
10.1016/j.cell.2015.08.037subject
Has Abstractpub_date
2015-09-24 00:00:00pages
230-45issue
1eissn
0092-8674issn
1097-4172pii
S0092-8674(15)01089-2journal_volume
163pub_type
杂志文章相关文献
CELL文献大全abstract::Many organs are composed of epithelial tubes that transport vital fluids. Such tubular organs develop in many different ways and generate tubes of widely varying sizes and structures, but always with the apical epithelial surface lining the lumen. We describe recent progress in several diverse cell culture and genetic...
journal_title:Cell
pub_type: 杂志文章,评审
doi:10.1016/s0092-8674(02)01283-7
更新日期:2003-01-10 00:00:00
abstract::RNA polymerase II (RNAPII) lies at the core of dynamic control of gene expression. Using 53 RNAPII point mutants, we generated a point mutant epistatic miniarray profile (pE-MAP) comprising ∼60,000 quantitative genetic interactions in Saccharomyces cerevisiae. This analysis enabled functional assignment of RNAPII subd...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2013.07.033
更新日期:2013-08-15 00:00:00
abstract::We show that transfer of human fibroblast chromosome 11 (containing the human MyoD gene) from primary cells into 10T1/2 mouse fibroblasts by microcell fusion activates expression of the transferred human MyoD gene and converts these cells to myoblasts. Transfer of human chromosome 11 into B78 melanoma cells also leads...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(90)90285-m
更新日期:1990-10-05 00:00:00
abstract::The formation of morphogen gradients is essential for tissue patterning. Morphogens are released from producing cells and spread through adjacent tissue; paradoxically, however, many morphogens, including Wingless, associate tightly with the cell membrane. Here, we describe a novel cell biological mechanism that dispe...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(01)00484-6
更新日期:2001-09-07 00:00:00
abstract::Production of nerve growth factor (NGF) was assessed in cultures of human T and B lymphocytes and macrophages. NGF was constitutively produced by B cells only, which also expressed surface p140trk-A and p75NGFR molecules and hence efficiently bound and internalized the cytokine. Neutralization of endogenous NGF caused...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(00)81113-7
更新日期:1996-05-03 00:00:00
abstract::Here we characterize the T-cell-activating protein (TAP), an Ly-6 gene product involved in T cell activation, as a glycoprotein with a molecular weight of 10-12 kd under nonreducing conditions and 15-18 kd under reducing ones. Two of the three bands that are precipitated from metabolically labeled cells are expressed ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(86)90593-3
更新日期:1986-11-07 00:00:00
abstract::The minimal DNA sequence required for the formation of a stable complex with Drosophila heat shock factor (HSF) in vitro is an inverted repeat of a 5 bp recognition unit, -GAA-. Surprisingly, both permutations of this 5 bp unit, head-to-head and tail-to-tail, bind to HSF with similar affinity and with striking 2-fold ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(89)90603-x
更新日期:1989-12-01 00:00:00
abstract::HNF-3 beta, a transcription factor of the winged-helix family, is expressed in embryonic and adult endoderm and also in midline cells of the node, notochord, and floor plate in mouse embryos. To define the function of HNF-3 beta, a targeted mutation in the HNF-3 beta locus was generated by homologous recombination in ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(94)90523-1
更新日期:1994-08-26 00:00:00
abstract::CRISPR-Cas9 is a versatile genome editing technology for studying the functions of genetic elements. To broadly enable the application of Cas9 in vivo, we established a Cre-dependent Cas9 knockin mouse. We demonstrated in vivo as well as ex vivo genome editing using adeno-associated virus (AAV)-, lentivirus-, or parti...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2014.09.014
更新日期:2014-10-09 00:00:00
abstract::To determine whether phylogenetically conservative H-Y antigen plays any part in gonadal differentiation among the nonmammalian vertebrates, we studied expression and binding of H-Y in the frog, Xenopus laevis. Soluble H-Y obtained from mouse testis and soluble H-W from chicken ovary bound specifically to cells of the...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(80)90332-3
更新日期:1980-07-01 00:00:00
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...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(00)81050-8
更新日期:1996-03-08 00:00:00
abstract::We have isolated three alleles of a novel Drosophila clock gene, double-time (dbt). Short- (dbtS) and long-period (dbtL) mutants alter both behavioral rhythmicity and molecular oscillations from previously identified clock genes, period and timeless. A third allele, dbtP, causes pupal lethality and eliminates circadia...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(00)81224-6
更新日期:1998-07-10 00:00:00
abstract::The archetypal human tumor suppressor p53 is considered to have unique transactivation properties. The assumption is based on the fact that additionally identified human p53 isoforms lack transcriptional activity. However, we provide evidence for the existence of an alternatively spliced p53 isoform (Deltap53) that ex...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2005.04.032
更新日期:2005-07-15 00:00:00
abstract::RNA-guided Cas9 endonucleases protect bacteria from viral infection and have been creatively repurposed as programmable molecular scalpels for surgical manipulation of DNA. Now, two papers in Cell (Pawluk et al. and Rauch et al.) identify viral proteins that suppress Cas9 and may function like molecular sheaths for th...
journal_title:Cell
pub_type: 评论,杂志文章
doi:10.1016/j.cell.2016.12.007
更新日期:2017-01-12 00:00:00
abstract::Synthesis of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], a signaling phospholipid, is primarily carried out by phosphatidylinositol 4-phosphate 5-kinase [PI(4)P5K], which has been reported to be regulated by RhoA and Rac1. Unexpectedly, we find that the GTPgammaS-dependent activator of PI(4)P5Kalpha is the smal...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(00)81540-8
更新日期:1999-11-24 00:00:00
abstract::Little is known about how neutrophils and other cells establish a single zone of actin assembly during migration. A widespread assumption is that the leading edge prevents formation of additional fronts by generating long-range diffusible inhibitors or by sequestering essential polarity components. We use morphologica...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2011.10.050
更新日期:2012-01-20 00:00:00
abstract::The activation of the tumor suppressor p53 facilitates the cellular response to genotoxic stress; however, the p53 response can only be executed if its interaction with its inhibitor Mdm2 is abolished. There have been conflicting reports on the question of whether p53 posttranslational modifications, such as phosphory...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2008.03.025
更新日期:2008-05-16 00:00:00
abstract::Ventral midline cells at different rostrocaudal levels of the central nervous system exhibit distinct properties but share the ability to pattern the dorsoventral axis of the neural tube. We show here that ventral midline cells acquire distinct identities in response to the different signaling activities of underlying...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(00)80334-7
更新日期:1997-07-25 00:00:00
abstract::In this issue of Cell, Korber et al. found that a SARS-CoV-2 variant in the spike protein D614G rapidly became dominant around the world. Although clinical and in vitro data suggest that D614G changes the virus phenotype, the impact of the mutation on transmission, disease, and vaccine and therapeutic development are ...
journal_title:Cell
pub_type: 评论,杂志文章
doi:10.1016/j.cell.2020.06.040
更新日期:2020-08-20 00:00:00
abstract::In normal human fibroblasts, the synthesis of a cell surface receptor for plasma low density lipoprotein (LDL) is regulated by a sensitive system of feedback suppression. The number of functional LDL receptors declines by more than 20 fold when cellular stores of esterified cholesterol are increased by incubation of c...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(76)90110-0
更新日期:1976-10-01 00:00:00
abstract::In cells of the B-lymphocyte lineage, 8.4 kb transcripts are constitutively produced from unrearranged kappa constant region (kappa 0) loci. To help elucidate the molecular basis of this phenomenon, we have determined the nucleotide sequence surrounding the site of transcriptional initiation. The kappa 0 transcripts a...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(81)90401-3
更新日期:1981-12-01 00:00:00
abstract::Most of the Dictyostelium ribosomal nontranscribed spacer DNA has been mapped using Eco R1, Hind III, and Sal I restriction digests and recombinant plasmids containing parts of the rDNA (ribosomal DNA). The repeat units are at least 42 kb (1 kilobase = 1000 base pairs = 1 kb) long; of this, 8 kb codes for the 36S rRNA...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(76)90043-x
更新日期:1976-12-01 00:00:00
abstract::Fragile X syndrome results from the expansion of a CGG repeat that is normally interrupted by occasional AGG triplets. Linkage disequilibrium suggests that certain normal haplotypes may contribute unequally to the pool of fragile X chromosomes. Sequence analysis of normal alleles demonstrates haplotype-specific variat...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(94)90134-1
更新日期:1994-06-17 00:00:00
abstract::NRK fibroblasts exposed to transforming growth factor-beta (TGF-beta) show increased binding of radiolabeled epidermal growth factor (EGF) relative to untreated cells. The binding of another growth factor, rat insulin-like growth factor-II, is unaffected. The increase in EGF binding induced by TGF-beta is not due to i...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(84)90071-0
更新日期:1984-01-01 00:00:00
abstract::The nucleus is connected to the cytoskeleton, and these connections are involved in multiple functions such as nuclear positioning, shape and stiffness, cytoskeleton organization, mechanotransduction, gene expression, chromosome positioning, DNA repair, and cell migration. ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2017.05.014
更新日期:2017-05-18 00:00:00
abstract::We describe a new repressible binary expression system based on the regulatory genes from the Neurospora qa gene cluster. This "Q system" offers attractive features for transgene expression in Drosophila and mammalian cells: low basal expression in the absence of the transcriptional activator QF, high QF-induced expre...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2010.02.025
更新日期:2010-04-30 00:00:00
abstract::Protein-DNA binding is mediated by the recognition of the chemical signatures of the DNA bases and the 3D shape of the DNA molecule. Because DNA shape is a consequence of sequence, it is difficult to dissociate these modes of recognition. Here, we tease them apart in the context of Hox-DNA binding by mutating residues...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2015.02.008
更新日期:2015-04-09 00:00:00
abstract::The COVID-19 pandemic has led to extensive morbidity and mortality throughout the world. Clinical features that drive SARS-CoV-2 pathogenesis in humans include inflammation and thrombosis, but the mechanistic details underlying these processes remain to be determined. In this study, we demonstrate endothelial disrupti...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2020.10.005
更新日期:2020-11-25 00:00:00
abstract::NF-kappa B is a nuclear protein, found only in cells that transcribe immunoglobulin light chain genes, that interacts with a defined site in the kappa immunoglobulin enhancer. This protein can be induced in pre-B cells by stimulation with bacterial lipopolysaccharide (LPS). The induction involves a posttranslational a...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(86)90807-x
更新日期:1986-12-26 00:00:00
abstract::Acquisition of the ability to produce and respond to a growth factor may result in increased cellular proliferation and could lead to malignant transformation. The fact that a large variety of tumor cells secrete transforming growth factor-alpha (TGF-alpha) suggests involvement of TGF-alpha in cellular transformation ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(86)90747-6
更新日期:1986-07-18 00:00:00