Abstract:
:Histone H3K4 methylation is an epigenetic mark associated with actively transcribed genes. This modification is catalyzed by the mixed lineage leukaemia (MLL) family of histone methyltransferases including MLL1, MLL2, MLL3, MLL4, SET1A and SET1B. The catalytic activity of this family is dependent on interactions with additional conserved proteins, but the structural basis for subunit assembly and the mechanism of regulation is not well understood. We used a hybrid methods approach to study the assembly and biochemical function of the minimally active MLL1 complex (MLL1, WDR5 and RbBP5). A combination of small angle X-ray scattering, cross-linking mass spectrometry, nuclear magnetic resonance spectroscopy and computational modeling were used to generate a dynamic ensemble model in which subunits are assembled via multiple weak interaction sites. We identified a new interaction site between the MLL1 SET domain and the WD40 β-propeller domain of RbBP5, and demonstrate the susceptibility of the catalytic function of the complex to disruption of individual interaction sites.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Kaustov L,Lemak A,Wu H,Faini M,Fan L,Fang X,Zeng H,Duan S,Allali-Hassani A,Li F,Wei Y,Vedadi M,Aebersold R,Wang Y,Houliston S,Arrowsmith CHdoi
10.1093/nar/gkz697subject
Has Abstractpub_date
2019-09-26 00:00:00pages
9433-9447issue
17eissn
0305-1048issn
1362-4962pii
5545732journal_volume
47pub_type
杂志文章abstract::Protein-protein and protein-DNA/RNA interactions play a fundamental role in a variety of biological processes. Determining the complex structures of these interactions is valuable, in which molecular docking has played an important role. To automatically make use of the binding information from the PDB in docking, her...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkx407
更新日期:2017-07-03 00:00:00
abstract::Archival formalin-fixed, paraffin-embedded and ethanol-fixed tissues represent a potentially invaluable resource for gene expression analysis, as they are the most widely available material for studies of human disease. Little data are available evaluating whether RNA obtained from fixed (archival) tissues could produ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/30.2.e4
更新日期:2002-01-15 00:00:00
abstract::Pathbase is a database that stores images of the abnormal histology associated with spontaneous and induced mutations of both embryonic and adult mice including those produced by transgenesis, targeted mutagenesis and chemical mutagenesis. Images of normal mouse histology and strain-dependent background lesions are al...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkh124
更新日期:2004-01-01 00:00:00
abstract::Ribosome assembly is a process fundamental for all cellular activities. The efficiency and accuracy of the subunit assembly are tightly regulated and closely monitored. In the present work, we characterized, both compositionally and structurally, a set of in vivo 50S subunit precursors (45S), isolated from a mutant ba...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkt423
更新日期:2013-08-01 00:00:00
abstract::NF-IL6beta regulates gene expression and plays function roles in many tissues. The EGF-regulated cyclooxygenase-2 (cox-2) expression is mediated through p38(MAPK) signaling pathway and positively correlates with NF-IL6beta expression in A431 cells. NF-IL6beta coordinated with c-Jun on cox-2 transcriptional activation ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkj422
更新日期:2006-01-05 00:00:00
abstract::Each of the major U snRNP polypeptides from human cells was purified by electroelution from SDS-polyacrylamide gels. Rabbit antisera could be obtained against the individual proteins 70K, A, B', B and D, although rabbits failed to elicit antibodies against E, F and G. A strong structural homology was found between pro...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/15.10.4021
更新日期:1987-05-26 00:00:00
abstract::Gene transfer and expression in eukaryotes is often limited by a number of stably maintained gene copies and by epigenetic silencing effects. Silencing may be limited by the use of epigenetic regulatory sequences such as matrix attachment regions (MAR). Here, we show that successive transfections of MAR-containing vec...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkr436
更新日期:2011-08-01 00:00:00
abstract::Bacteriophage DNA packaging motors translocate their genomic DNA into viral heads, compacting it to near-crystalline density. The Bacillus subtilis phage 29 has a unique ring of RNA (pRNA) that is an essential component of its motor, serving as a scaffold for the packaging ATPase. Previously, deletion of a three-base ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks724
更新日期:2012-10-01 00:00:00
abstract::Rapid and transient activation of both c-fos transcription and mRNA accumulation occurs when resting CCL39 hamster fibroblasts are serum-stimulated to grow. By using several combinations of serum and cycloheximide, a protein synthesis inhibitor, we showed that: i) addition of cycloheximide to resting cell elicits an i...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/15.14.5657
更新日期:1987-07-24 00:00:00
abstract::The alternatively spliced RNA species of tumor suppressor gene p53, containing an additional 96 bases derived from intron 10, is present at approximately 25 to 30% the level of regularly spliced p53 RNA in both normal epidermal and carcinoma cells. The presence of this alternatively spliced RNA in 10T1/2 fibroblast ce...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/20.8.1979
更新日期:1992-04-25 00:00:00
abstract::Genome-wide association studies (GWAS) have become a preferred method to identify new genetic susceptibility loci. This technique aims to understanding the molecular etiology of common diseases, but in many cases, it has led to the identification of loci with no obvious biological relevance. Herein, we show that previ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks169
更新日期:2012-06-01 00:00:00
abstract::The cDNA encoding Chinese hamster O6-alkylguanine-DNA-alkyltransferase (ATase) has been isolated from a library prepared from RNA isolated from V79 lung fibroblasts which had an upregulated level of this repair activity following stepwise selection with a chloroethylating agent (1, 2). Expression of the cDNA in E. col...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/20.8.1891
更新日期:1992-04-25 00:00:00
abstract::Work from a number of laboratories has indicated that the TATA box sequence can act as a basal promoter element not only for RNA polymerase II (RNAP II) transcription, but also for transcription by RNA polymerase III (RNAP III). We previously reported that, in the absence of other cis-acting elements, the canonical TA...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/24.15.3100
更新日期:1996-08-01 00:00:00
abstract::BioModels Database (http://www.ebi.ac.uk/biomodels/), part of the international initiative BioModels.net, provides access to published, peer-reviewed, quantitative models of biochemical and cellular systems. Each model is carefully curated to verify that it corresponds to the reference publication and gives the proper...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkj092
更新日期:2006-01-01 00:00:00
abstract::The anti-cancer drug 2',2'-difluoro-2'-deoxycytidine (dFdC) is internally incorporated into DNA in vitro. To determine the effects of this incorporation on DNA structure and function, the beta-cyanoethyl phosphoramidite of dFdC was synthesized and oligodeoxyribonucleotides containing dFdC were made using automated sol...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/20.7.1763
更新日期:1992-04-11 00:00:00
abstract::Various strategies employed in genomic DNA cloning by subtractive hybridization have been examined by computer simulations, with the comparison between the predictions and the published results. The result shows that the efficiency of target sequence enrichment and the sensitivity to experimental conditions depend str...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/26.6.1440
更新日期:1998-03-15 00:00:00
abstract::Current DNA assembly methods for preparing highly purified linear subassemblies require complex and time-consuming in vitro manipulations that hinder their ability to construct megabase-sized DNAs (e.g. synthetic genomes). We have developed a new method designated 'CasHRA (Cas9-facilitated Homologous Recombination Ass...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkw475
更新日期:2016-08-19 00:00:00
abstract::Lambda-red system-based recombinogenic engineering is a powerful new method to engineer DNA without the need for restriction enzymes or ligases. Here, we report the use of a single selectable marker to enhance the usefulness of this approach. The strategy is to utilize the thymidylate synthase A (thyA) gene, which enc...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gni059
更新日期:2005-03-30 00:00:00
abstract::In most bacteria, two tRNAs decode the four arginine CGN codons. One tRNA harboring a wobble inosine (tRNA(Arg)ICG) reads the CGU, CGC and CGA codons, whereas a second tRNA harboring a wobble cytidine (tRNA(Arg)CCG) reads the remaining CGG codon. The reduced genomes of Mycoplasmas and other Mollicutes lack the gene en...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkt356
更新日期:2013-07-01 00:00:00
abstract::The Structural Classification of Proteins (SCOP) database provides a detailed and comprehensive description of the relationships of known protein structures. The classification is on hierarchical levels: the first two levels, family and superfamily, describe near and distant evolutionary relationships; the third, fold...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/28.1.257
更新日期:2000-01-01 00:00:00
abstract::RNA sequencing (RNA-Seq) is a powerful tool for analyzing the identity of cellular RNAs but is often limited by the amount of material available for analysis. In spite of extensive efforts employing existing protocols, we observed that it was not possible to obtain useful sequencing libraries from nuclear RNA derived ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkv213
更新日期:2015-06-23 00:00:00
abstract::In plant organelles, RNA editing alters specific cytidine residues to uridine in transcripts. All of the site-specificity factors of RNA editing identified so far are pentatricopeptide repeat (PPR) proteins. A defect in a specific PPR protein often impairs RNA editing at multiple sites, at which the cis-acting element...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks164
更新日期:2012-06-01 00:00:00
abstract::Oligoribonucleotides with 2'-5' linkages have been synthesized on solid support. UV melting and CD experiments indicate complementary strands associate to give complexes with melting temperatures 30 to 40 degrees C lower than for duplexes formed by 3'-5' oligoribonucleotides with the same sequence. UV melting and imin...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/20.7.1685
更新日期:1992-04-11 00:00:00
abstract::Bacterial RNase III plays important roles in the processing and degradation of RNA transcripts. A major goal is to identify the cleavage targets of this endoribonuclease at a transcriptome-wide scale and delineate its in vivo cleavage rules. Here we applied to Escherichia coli grown to either exponential or stationary...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky684
更新日期:2018-11-02 00:00:00
abstract::The RNA-dependent RNA polymerases (RdRPs) encoded by RNA viruses represent a unique class of nucleic acid polymerases. RdRPs are essential in virus life cycle due to their central role in viral genome replication/transcription processes. However, their contribution in host adaption has not been well documented. By sol...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa1250
更新日期:2021-01-06 00:00:00
abstract::Proteins that bind to DNA are found in all areas of genetic activity within the cell. To help understand how these proteins perform their various functions, it is useful to analyse which residues are involved in binding to the DNA and how they interact with the bases and sugar-phosphate backbone of nucleic acids. Here...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/25.24.4940
更新日期:1997-12-15 00:00:00
abstract::Atomistic molecular dynamics (MD) simulations generate a wealth of information related to the dynamics of proteins. If properly analyzed, this information can lead to new insights regarding protein function and assist wet-lab experiments. Aiming to identify interactions between individual amino acid residues and the r...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky381
更新日期:2018-07-02 00:00:00
abstract::Targeted differentiation of human induced pluripotent stem cells (hiPSCs) using only chemicals would have value-added clinical potential in the regeneration of complex cell types including cardiomyocytes. Despite the availability of several chemical inhibitors targeting proteins involved in signaling pathways, no bioa...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkx693
更新日期:2017-09-19 00:00:00
abstract::We have used in vitro transcription in isolated pea nuclei to determine whether the expression of genes for the seed storage proteins legumin and vicilin is regulated transcriptionally or post-transcriptionally in response to changing sulfur status in the developing seed. During the first 48 h of recovery from S defic...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/13.3.999
更新日期:1985-02-11 00:00:00
abstract::eggNOG is a public database of orthology relationships, gene evolutionary histories and functional annotations. Here, we present version 5.0, featuring a major update of the underlying genome sets, which have been expanded to 4445 representative bacteria and 168 archaea derived from 25 038 genomes, as well as 477 euka...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky1085
更新日期:2019-01-08 00:00:00