Abstract：
:Polycomb repressive complex 2 (PRC2) catalyzes methylation on lysine 27 of histone H3 (H3K27) and is required for maintaining transcriptional patterns and cellular identity, but the specification and maintenance of genomic PRC2 binding and H3K27 methylation patterns remain incompletely understood. Epigenetic mechanisms have been proposed, wherein pre-existing H3K27 methylation directs recruitment and regulates the catalytic activity of PRC2 to support its own maintenance. Here we investigate whether such mechanisms are required for specifying H3K27 methylation patterns in mouse embryonic stem cells (mESCs). Through re-expression of PRC2 subunits in PRC2-knockout cells that have lost all H3K27 methylation, we demonstrate that methylation patterns can be accurately established de novo. We find that regional methylation kinetics correlate with original methylation patterns even in their absence, and specification of the genomic PRC2 binding pattern is retained and specifically dependent on the PRC2 core subunit SUZ12. Thus, the H3K27 methylation patterns in mESCs are not dependent on self-autonomous epigenetic inheritance.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
Højfeldt JW,Laugesen A,Willumsen BM,Damhofer H,Hedehus L,Tvardovskiy A,Mohammad F,Jensen ON,Helin Kdoi
10.1038/s41594-018-0036-6subject
Has Abstractpub_date
2018-03-01 00:00:00pages
225-232issue
3eissn
1545-9993issn
1545-9985pii
10.1038/s41594-018-0036-6journal_volume
25pub_type
杂志文章abstract：:HIV-1 capsid plays multiple key roles in viral replication, and inhibition of capsid assembly is an attractive target for therapeutic intervention. Here, we report the atomic-resolution structure of capsid protein (CA) tubes, determined by magic-angle spinning NMR and data-guided molecular dynamics simulations. Functi...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/s41594-020-0489-2
更新日期：2020-09-01 00:00:00
abstract：:Allosteric interactions are typically considered to proceed through a series of discrete changes in bonding interactions that alter the protein conformation. Here we show that allostery can be mediated exclusively by transmitted changes in protein motions. We have characterized the negatively cooperative binding of cA...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb1132
更新日期：2006-09-01 00:00:00
abstract：:Mosquito-based malaria transmission-blocking vaccines (mTBVs) target midgut-surface antigens of the Plasmodium parasite's obligate vector, the Anopheles mosquito. The alanyl aminopeptidase N (AnAPN1) is the leading mTBV immunogen; however, AnAPN1's role in Plasmodium infection of the mosquito and how anti-AnAPN1 antib...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.3048
更新日期：2015-07-01 00:00:00
abstract：:Maintenance of cell volume against osmotic change is crucial for proper cell functions. Leucine-rich repeat-containing 8 proteins are anion-selective channels that extrude anions to decrease the cell volume on cellular swelling. Here, we present the structure of human leucine-rich repeat-containing 8A, determined by s...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/s41594-018-0109-6
更新日期：2018-09-01 00:00:00
abstract：:The noncoding RNA Xist recruits silencing factors to the inactive X chromosome (Xi) and facilitates re-organization of Xi structure. Here, we examine the mouse epigenomic landscape of Xi and assess how Xist alters chromatin accessibility. Xist deletion triggers a gain of accessibility of select chromatin regions that ...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/s41594-018-0176-8
更新日期：2019-02-01 00:00:00
abstract：:DNA ligases finalize DNA replication and repair through DNA nick-sealing reactions that can abort to generate cytotoxic 5'-adenylation DNA damage. Aprataxin (Aptx) catalyzes direct reversal of 5'-adenylate adducts to protect genome integrity. Here the structure of a Schizosaccharomyces pombe Aptx-DNA-AMP-Zn(2+) comple...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.2146
更新日期：2011-10-09 00:00:00
abstract：:Suppressing cellular signal transducers of transcription 2 (STAT2) is a common strategy that viruses use to establish infections, yet the detailed mechanism remains elusive, owing to a lack of structural information about the viral-cellular complex involved. Here, we report the cryo-EM and crystal structures of human ...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/s41594-020-0472-y
更新日期：2020-10-01 00:00:00
abstract：:The eukaryotic DNA replication machinery must traverse every nucleosome in the genome during S phase. As nucleosomes are generally inhibitory to DNA-dependent processes, chromatin structure must undergo extensive reorganization to facilitate DNA synthesis. However, the identity of chromatin-remodeling factors involved...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.1419
更新日期：2008-05-01 00:00:00
abstract：:Aquaporin (AQP) folding in the endoplasmic reticulum is characterized by two distinct pathways of membrane insertion that arise from divergent residues within the second transmembrane segment. We now show that in AQP1 these residues (Asn49 and Lys51) interact with Asp185 at the C terminus of TM5 to form a polar, quate...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb1275
更新日期：2007-08-01 00:00:00
abstract：:Clustered codons that pair to low-abundance tRNA isoacceptors can form slow-translating regions in the mRNA and cause transient ribosomal arrest. We report that folding efficiency of the Escherichia coli multidomain protein SufI can be severely perturbed by alterations in ribosome-mediated translational attenuation. S...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.1554
更新日期：2009-03-01 00:00:00
abstract：:Ribosomes catalyze the formation of peptide bonds between aminoacyl esters of transfer RNAs within a catalytic center composed of ribosomal RNA only. Here we show that the reaction of P-site formylmethionine (fMet)-tRNA(fMet) with a modified A-site tRNA substrate, Phelac-tRNA(Phe), in which the nucleophilic amino grou...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb1091
更新日期：2006-05-01 00:00:00
abstract：:Jun dimerization protein-2 (JDP2) is a component of the AP-1 transcription factor that represses transactivation mediated by the Jun family of proteins. Here, we examine the functional mechanisms of JDP2 and show that it can inhibit p300-mediated acetylation of core histones in vitro and in vivo. Inhibition of histone...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb1063
更新日期：2006-04-01 00:00:00
abstract：:Integrins are heterodimeric cell-surface adhesion molecules comprising one of 18 possible α-chains and one of eight possible β-chains. They control a range of cell functions in a matrix- and ligand-specific manner. Integrins can be internalized by clathrin-mediated endocytosis (CME) through β subunit-based motifs foun...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.3161
更新日期：2016-02-01 00:00:00
abstract：:Interactions between Src homology 2 (SH2) domains and phosphotyrosine sites regulate tyrosine kinase signaling networks. Selective perturbation of these interactions is challenging due to the high homology among the 120 human SH2 domains. Using an improved phage-display selection system, we generated a small antibody ...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.1793
更新日期：2010-04-01 00:00:00
abstract：:Multiple Argonaute proteins are implicated in gene silencing by RNA interference (RNAi), but only one is known to be an endonuclease that can cleave target mRNAs. Chimeric Argonaute proteins now reveal an unexpected mechanism by which mutations distal to the catalytic center can unmask intrinsic catalytic activity, re...
journal_title：Nature structural & molecular biology
pub_type： 评论,新闻
doi：10.1038/nsmb.2620
更新日期：2013-07-01 00:00:00
abstract：:The interaction of autotaxin with its substrates leads to the production of lysophosphatidic acids (LPA), bioactive lipids with an emerging prominent role in inflammation and cancer. Two papers in this issue tell the previously unknown story of autotaxin, from substrate discrimination to highly efficient local deliver...
journal_title：Nature structural & molecular biology
pub_type： 评论,杂志文章
doi：10.1038/nsmb0211-117
更新日期：2011-02-01 00:00:00
abstract：:Complex forms of cellular motility, including cell division, organelle trafficking or signal amplification in the auditory system, require strong coordination of the myosin motors involved. The most basic mechanism of coordination is via direct mechanical interactions of individual motor heads leading to modification ...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.1820
更新日期：2010-05-01 00:00:00
abstract：:The core of the neurotransmitter release machinery is formed by SNARE complexes, which bring the vesicle and plasma membranes together and are key for fusion, and by Munc18-1, which controls SNARE-complex formation and may also have a direct role in fusion. In addition, SNARE complex assembly is likely orchestrated by...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章,评审
doi：10.1038/nsmb.1450
更新日期：2008-07-01 00:00:00
abstract：:Beta-2 microglobulin (beta2m) is a globular protein that self-associates into fibrillar amyloid deposits in patients undergoing hemodialysis therapy. Formation of these beta-sheet-rich assemblies is a fundamental property of polypeptides that can be triggered by diverse conditions. For beta2m, oligomerization into pre...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.1483
更新日期：2008-09-01 00:00:00
abstract：:The WAVE regulatory complex (WRC) transmits information from the Rac GTPase to the actin nucleator Arp2/3 complex. We have reconstituted recombinant human and Drosophila WRC in several forms and shown that they are inactive toward Arp2/3 complex but can be activated by Rac in a nucleotide-dependent fashion. Our observ...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.1587
更新日期：2009-05-01 00:00:00
abstract：:During protein synthesis, mRNA and tRNAs are iteratively translocated by the ribosome. Precisely what molecular event is rate limiting for translocation is not known. Here we show that disruption of the interactions between the A-site codon and the ribosome accelerates translocation, suggesting that the release of the...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.2140
更新日期：2011-10-23 00:00:00
abstract：:Eukaryotic elongation factor-1 (eEF1) is essential for peptide-chain elongation during translation. We report that its gamma subunit (eEF1Bgamma) specifically binds, and bundles, keratin intermediate filaments. Disrupting this interaction depresses translation by approximately 20% and selectively increases 80S ribosom...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb1301
更新日期：2007-10-01 00:00:00
abstract：:Messenger RNAs produced by splicing are translated more efficiently than those produced from similar intronless precursor mRNAs (pre-mRNAs). The exon-junction complex (EJC) probably mediates this enhancement; however, the specific link between the EJC and the translation machinery has not been identified. The EJC prot...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb1321
更新日期：2007-12-01 00:00:00
abstract：:Celiac disease is a T cell-mediated disease induced by dietary gluten, a component of which is gliadin. 95% of individuals with celiac disease carry the HLA (human leukocyte antigen)-DQ2 locus. Here we determined the T-cell receptor (TCR) usage and fine specificity of patient-derived T-cell clones specific for two epi...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.2817
更新日期：2014-05-01 00:00:00
abstract：:The eukaryotic exosome is a multisubunit complex typically composed of a catalytically inactive core and the Rrp44 protein, which contains 3'-to-5' exo- and endo-RNase activities. RNA substrates have been shown to be recruited through the core to reach Rrp44's exo-RNase (EXO) site. Using single-particle EM and biochem...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.2736
更新日期：2014-01-01 00:00:00
abstract：:Many classes of small RNA (sRNA) involved in RNA silencing are generated by double-stranded RNA (dsRNA) processing. Although principles of sRNA biogenesis have emerged, newly identified classes of sRNAs have features that suggest additional biogenesis mechanisms. Tetrahymena thermophila expresses one such class, compr...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb1262
更新日期：2007-07-01 00:00:00
abstract：:Tripeptidyl peptidase II (TPP II) is the largest known eukaryotic protease (6 MDa). It is believed to act downstream of the 26S proteasome, cleaving tripeptides from the N termini of longer peptides, and it is implicated in numerous cellular processes. Here we report the structure of Drosophila TPP II determined by a ...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.1870
更新日期：2010-08-01 00:00:00
abstract：:During homologous recombination, Rad51 forms a nucleoprotein filament with single-stranded DNA (ssDNA) that undergoes strand exchange with homologous double-stranded DNA (dsDNA). Here, we use real-time analysis to show that strand exchange by fission yeast Rad51 proceeds via two distinct three-strand intermediates, C1...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/s41594-017-0002-8
更新日期：2018-01-01 00:00:00
abstract：:Previous studies have linked the C-terminal domain (CTD) of RNA polymerase II (pol II) with cotranscriptional precursor messenger RNA processing, but little is known about the CTD's function in regulating alternative splicing. We have examined this function using alpha-amanitin-resistant pol II CTD mutants and fibrone...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb1155
更新日期：2006-11-01 00:00:00
abstract：:In bacteria, incorporation of selenocysteine, the 21(st) amino acid, into proteins requires elongation factor SelB, which has the unusual property of binding to both transfer RNA (tRNA) and mRNA. SelB binds to an mRNA hairpin formed by the selenocysteine insertion sequence (SECIS) with extremely high specificity, the ...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb890
更新日期：2005-02-01 00:00:00
