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 subdomains and uncovered connections between individual regions and other protein complexes. Using splicing microarrays and mutants that alter elongation rates in vitro, we found an inverse relationship between RNAPII speed and in vivo splicing efficiency. Furthermore, the pE-MAP classified fast and slow mutants that favor upstream and downstream start site selection, respectively. The striking coordination of polymerization rate with transcription initiation and splicing suggests that transcription rate is tuned to regulate multiple gene expression steps. The pE-MAP approach provides a powerful strategy to understand other multifunctional machines at amino acid resolution.
journal_name
Celljournal_title
Cellauthors
Braberg H,Jin H,Moehle EA,Chan YA,Wang S,Shales M,Benschop JJ,Morris JH,Qiu C,Hu F,Tang LK,Fraser JS,Holstege FC,Hieter P,Guthrie C,Kaplan CD,Krogan NJdoi
10.1016/j.cell.2013.07.033subject
Has Abstractpub_date
2013-08-15 00:00:00pages
775-88issue
4eissn
0092-8674issn
1097-4172pii
S0092-8674(13)00938-0journal_volume
154pub_type
杂志文章相关文献
CELL文献大全abstract::Cellular receptors are required for efficient entry of retroviruses into cells. We previously cloned a chicken gene responsible for susceptibility to the retrovirus subgroup A Rous sarcoma virus (RSV(A)). Here we have isolated the quail homolog and generated two alternatively spliced processed genes encoding cellular ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(93)90726-7
更新日期:1993-09-24 00:00:00
abstract::Hematopoietic stem cells (HSCs) exist in the bone marrow and circulate in the blood. In this issue, Massberg et al. (2007) report that HSCs also travel through the lymphatic system. Furthermore, migration of HSCs--which express Toll-like receptors--allows the recognition of pathogenic molecules in peripheral tissues t...
journal_title:Cell
pub_type: 评论,杂志文章
doi:10.1016/j.cell.2007.11.010
更新日期:2007-11-30 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::During development, neurons switch among growth states, such as initial axon outgrowth, axon pruning, and regrowth. By studying the stereotypic remodeling of the Drosophila mushroom body (MB), we found that the heme-binding nuclear receptor E75 is dispensable for initial axon outgrowth of MB γ neurons but is required ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2015.11.047
更新日期:2016-01-14 00:00:00
abstract::While developing an assay to measure the activity of the tat protein from human immunodeficiency virus 1 (HIV-1), we discovered that the purified protein could be taken up by cells growing in tissue culture and subsequently trans-activate the viral promoter. Trans-activation is dramatically increased by a variety of l...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(88)90263-2
更新日期:1988-12-23 00:00:00
abstract::The Viviparous-1 (Vp1) gene of maize is specifically required for expression of the maturation program in seed development. We show that Vp1 encodes a 73,335 dalton protein with no detectable homology to known proteins. An acidic transcriptional activation sequence was identified by fusion to the GAL4 DNA-binding doma...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(91)90436-3
更新日期:1991-09-06 00:00:00
abstract::Endogenous and infectious mouse mammary tumor viruses (MMTVs) encode in their 3' long terminal repeat a protein that exerts superantigen activity; that is, it is able to interact with T cells via the variable domain of the T cell receptor (TCR) beta chain. We show here that transmission of an infectious MMTV is preven...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(93)80054-i
更新日期:1993-08-13 00:00:00
abstract::The copy number of yeast histone genes was increased by inserting an extra H2A,H2B gene pair into the haploid genome by the technique of yeast transformation. The presence of this extra gene copy has no detectable effect on cell growth. The steady-state levels of histone H2A,H2B mRNAs are not elevated in transformed s...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(81)90327-5
更新日期:1981-05-01 00:00:00
abstract::Meyer et al. find that subjects lacking the AIRE gene, critical for self-tolerance in T lymphocytes, show a broad range of autoantibody specificities, which can have extremely high affinities. The data also suggest that some of these autoantibodies can, surprisingly, prevent some types of autoimmunity, particularly ty...
journal_title:Cell
pub_type: 评论,杂志文章
doi:10.1016/j.cell.2016.07.018
更新日期:2016-07-28 00:00:00
abstract::The crystal structure of the snake toxin fasciculin, bound to mouse acetylcholinesterase (mAChE), at 3.2 A resolution reveals a synergistic three-point anchorage consistent with the picomolar dissociation constant of the complex. Loop II of fasciculin contains a cluster of hydrophobic residues that interact with the p...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(95)90128-0
更新日期:1995-11-03 00:00:00
abstract::A growing body of evidence indicates that plant transcription factors move between cells. A recent paper by Nakajima et al. (2001) shows that movement of the SHORTROOT protein provides a mechanism for signaling positional information between cell layers of the root. ...
journal_title:Cell
pub_type: 杂志文章,评审
doi:10.1016/s0092-8674(01)00532-3
更新日期:2001-10-19 00:00:00
abstract::Most gram-negative pathogens express fibrous adhesive virulence organelles that mediate targeting to the sites of infection. The F1 capsular antigen from the plague pathogen Yersinia pestis consists of linear fibers of a single subunit (Caf1) and serves as a prototype for nonpilus organelles assembled via the chaperon...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(03)00351-9
更新日期:2003-05-30 00:00:00
abstract::Protein aggregation is linked with neurodegeneration and numerous other diseases by mechanisms that are not well understood. Here, we have analyzed the gain-of-function toxicity of artificial β sheet proteins that were designed to form amyloid-like fibrils. Using quantitative proteomics, we found that the toxicity of ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2010.11.050
更新日期:2011-01-07 00:00:00
abstract::Francis' office window (at the Salk) commanded a panorama of the Pacific. "This grand natural scene was a physical correlate of Francis's intellectual world: wide-ranging, brilliantly lit, a little overawing, but also immensely inviting and above all an exciting place to be." (Mitchison, 2004). ...
journal_title:Cell
pub_type: 传,历史文章,杂志文章
doi:10.1016/j.cell.2016.11.008
更新日期:2016-12-01 00:00:00
abstract::Nuclear matrices from undifferentiated and differentiated Friend erythroleukemia cells have been obtained by a method which removes DNA in a physiological buffer. These matrices preserved the characteristic topographical distribution of condensed and diffuse "chromatin" regions, as do nuclei in situ or isolated nuclei...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(79)90221-6
更新日期:1979-12-01 00:00:00
abstract::The yeast Sir2/3/4p complex is found in abundance at telomeres, where it participates in the formation of silent heterochromatin and telomere maintenance. Here, we show that Sir3p is released from telomeres in response to DNA double-strand breaks (DSBs), binds to DSBs, and mediates their repair, independent of cell ma...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(00)80772-2
更新日期:1999-05-28 00:00:00
abstract::We have shown that covalent conjugation of ubiquitin to proteins is temperature-sensitive in the mouse cell cycle mutant ts85 due to a specifically thermolabile ubiquitin-activating enzyme (accompanying paper). We show here that degradation of short-lived proteins is also temperature sensitive in ts85 , in contrast to...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(84)90300-3
更新日期:1984-05-01 00:00:00
abstract::V(D)J recombination of antigen receptor gene segments in B and T cells is mediated by the lymphoid-specific proteins RAG1 and RAG2. Now, Ji et al. (2010) demonstrate how RAG1 and RAG2 use DNA sequence specificity and modified histones within chromatin to target specific loci for V(D)J recombination at different stages...
journal_title:Cell
pub_type: 评论,杂志文章
doi:10.1016/j.cell.2010.04.014
更新日期:2010-04-30 00:00:00
abstract::Most human epithelial tumors harbor numerous alterations, making it difficult to predict which genes are required for tumor survival. To systematically identify cancer dependencies, we analyzed 501 genome-scale loss-of-function screens performed in diverse human cancer cell lines. We developed DEMETER, an analytical f...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2017.06.010
更新日期:2017-07-27 00:00:00
abstract::The functional consequences of glycan structural changes associated with cellular differentiation are ill defined. Herein, we investigate the role of glycan adducts to the O-glycosylated polypeptide stalk tethering the CD8alphabeta coreceptor to the thymocyte surface. We show that immature CD4(+)CD8(+) double-positive...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(01)00577-3
更新日期:2001-11-16 00:00:00
abstract::During RNA interference (RNAi), Dicer generates short interfering RNAs (siRNAs), which then guide target mRNA cleavage by the RISC complex. Now, Liu et al. identify R2D2, a Dicer-associated protein that is important for siRNA incorporation into RISC, thus linking the initiation and execution phases of RNAi. ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(03)00806-7
更新日期:2003-10-17 00:00:00
abstract::Type 2 (non-insulin-dependent) diabetes mellitus is a progressive metabolic disorder arising from genetic and environmental factors that impair beta cell function and insulin action in peripheral tissues. We identified reduced diacylglycerol kinase delta (DGKdelta) expression and DGK activity in skeletal muscle from t...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2007.12.035
更新日期:2008-02-08 00:00:00
abstract::Telomere capping is the essential function of telomeres. To identify new genes involved in telomere capping, we carried out a genome-wide screen in Saccharomyces cerevisiae for suppressors of cdc13-1, an allele of the telomere-capping protein Cdc13. We report the identification of five novel suppressors, including the...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2005.12.044
更新日期:2006-03-24 00:00:00
abstract::Repression of the yeast silent mating type loci requires cis-acting sequences located over 1 kb from the regulated promoters. One of these sites, a "silencer," exhibits enhancer-like distance- and orientation-independence. The silencer demonstrates both autonomous replication sequence (ARS) activity and a centromere-l...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(87)90094-8
更新日期:1987-12-04 00:00:00
abstract::As the pipeline of new antibiotics slows to a trickle, scientists are developing innovative strategies to unearth antibacterial compounds in unexpected places. ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2006.11.021
更新日期:2006-12-01 00:00:00
abstract::Chemotherapy results in a frequent yet poorly understood syndrome of long-term neurological deficits. Neural precursor cell dysfunction and white matter dysfunction are thought to contribute to this debilitating syndrome. Here, we demonstrate persistent depletion of oligodendrocyte lineage cells in humans who received...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2018.10.049
更新日期:2019-01-10 00:00:00
abstract::The initiation of transcription from the nitrogen-regulated promoter glnAp2 requires RNA polymerase containing sigma 54, the transcriptional activator NRI, and the protein kinase NRII, responsible for the conversion of NRI to the active NRI-phosphate. NRI-phosphate does not increase the ability of sigma 54-containing ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(87)90170-x
更新日期:1987-09-25 00:00:00
abstract::RECQL5 is the sole member of the RECQ family of helicases associated with RNA polymerase II (RNAPII). We now show that RECQL5 is a general elongation factor that is important for preserving genome stability during transcription. Depletion or overexpression of RECQL5 results in corresponding shifts in the genome-wide R...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2014.03.048
更新日期:2014-05-22 00:00:00
abstract::X-linked lissencephaly and "double cortex" are allelic human disorders mapping to Xq22.3-Xq23 associated with arrest of migrating cerebral cortical neurons. We identified a novel 10 kb brain-specific cDNA interrupted by a balanced translocation in an XLIS patient that encodes a novel 40 kDa predicted protein named Dou...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(00)80899-5
更新日期:1998-01-09 00:00:00
abstract::Transfer RNAs (tRNAs) are primarily viewed as static contributors to gene expression. By developing a high-throughput tRNA profiling method, we find that specific tRNAs are upregulated in human breast cancer cells as they gain metastatic activity. Through loss-of-function, gain-of-function, and clinical-association st...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2016.05.046
更新日期:2016-06-02 00:00:00