The Xist RNA-PRC2 complex at 20-nm resolution reveals a low Xist stoichiometry and suggests a hit-and-run mechanism in mouse cells.

Abstract:

:X-chromosome inactivation (XCI) is initiated by the long noncoding RNA Xist, which coats the inactive X (Xi) and targets Polycomb repressive complex 2 (PRC2) in cis. Epigenomic analyses have provided significant insight into Xist binding patterns and chromatin organization of the Xi. However, such epigenomic analyses are limited by averaging of population-wide dynamics and do not inform behavior of single cells. Here we view Xist RNA and the Xi at 20-nm resolution using STochastic Optical Reconstruction Microscopy (STORM) in mouse cells. We observe dynamics at the single-cell level not predicted by epigenomic analysis. Only ∼50 hubs of Xist RNA occur on the Xi in the maintenance phase, corresponding to 50-100 Xist molecules per Xi and contrasting with the chromosome-wide "coat" observed by deep sequencing and conventional microscopy. Likewise, only ∼50 hubs PRC2 are observed. PRC2 and Xist foci are not randomly distributed but showed statistically significant spatial association. Knock-off experiments enable visualization of the dynamics of dissociation and relocalization onto the Xi and support a functional tethering of Xist and PRC2. Our analysis reveals that Xist-PRC2 complexes are less numerous than expected and suggests methylation of nucleosomes in a hit-and-run model.

authors

Sunwoo H,Wu JY,Lee JT

doi

10.1073/pnas.1503690112

subject

Has Abstract

pub_date

2015-08-04 00:00:00

pages

E4216-25

issue

31

eissn

0027-8424

issn

1091-6490

pii

1503690112

journal_volume

112

pub_type

杂志文章
  • Direct reprogramming of mouse fibroblasts to neural progenitors.

    abstract::The simple yet powerful technique of induced pluripotency may eventually supply a wide range of differentiated cells for cell therapy and drug development. However, making the appropriate cells via induced pluripotent stem cells (iPSCs) requires reprogramming of somatic cells and subsequent redifferentiation. Given ho...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1103113108

    authors: Kim J,Efe JA,Zhu S,Talantova M,Yuan X,Wang S,Lipton SA,Zhang K,Ding S

    更新日期:2011-05-10 00:00:00

  • Effects of early intervention and the moderating effects of brain activity on institutionalized children's social skills at age 8.

    abstract::The present study examined the social skills of previously institutionalized, 8-y-old Romanian children from the Bucharest Early Intervention Project and the influence of attachment security and brain electrical activity (alpha power) on these skills. Participants included children randomized to an intervention involv...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章,随机对照试验

    doi:10.1073/pnas.1121256109

    authors: Almas AN,Degnan KA,Radulescu A,Nelson CA 3rd,Zeanah CH,Fox NA

    更新日期:2012-10-16 00:00:00

  • Galantamine: effect on nicotinic receptor binding, acetylcholinesterase inhibition, and learning.

    abstract::Classical eyeblink conditioning is a well-characterized model paradigm that engages the septohippocampal cholinergic system. This form of associative learning is impaired in normal aging and severely disrupted in Alzheimer's disease (AD). Some nicotinic cholinergic receptor subtypes are lost in AD, making the use of n...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.031584398

    authors: Woodruff-Pak DS,Vogel RW 3rd,Wenk GL

    更新日期:2001-02-13 00:00:00

  • On finitely additive vector measures.

    abstract::In this paper we extend the well-known Vitali-Hahn-Saks and Nikodým theorems for measures to finitely additive vector-valued set functions. ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.67.3.1294

    authors: Brooks JK,Jewett RS

    更新日期:1970-11-01 00:00:00

  • Specific binding of leukotriene C4 to ileal segments and subcellular fractions of ileal smooth muscle cells.

    abstract::A specific high-affinity receptor for leukotriene C4 (LTC4) has been identified on segments of longitudinal smooth muscle from guinea pig ileum, in disrupted cells obtained from the ileal segments, and in subcellular fractions enriched for mitochondrial membranes and plasma membranes, respectively. Specific [3H]LTC4 b...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.81.14.4529

    authors: Krilis S,Lewis RA,Corey EJ,Austen KF

    更新日期:1984-07-01 00:00:00

  • Related cell-surface antigens expressed with positional specificity in Drosophila imaginal discs.

    abstract::We have isolated three classes of monoclonal antibodies against Drosophila cell-surface antigens that are expressed with positional specificity in imaginal discs. Comparison of immunofluorescence patterns with the wing-disc fate map reveals that expression of the antigens is not directly related to the specific type o...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.81.23.7485

    authors: Brower DL,Wilcox M,Piovant M,Smith RJ,Reger LA

    更新日期:1984-12-01 00:00:00

  • High-throughput approach for detection of DNA bending and flexibility based on cyclization.

    abstract::We have developed a high-throughput approach to the labor-intensive problems of DNA cyclization, which we use to characterize DNA curvature and mechanical properties. The method includes a combinatorial approach to make the DNA constructs needed and automated real-time measurement of the kinetics using fluorescence. W...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0530189100

    authors: Zhang Y,Crothers DM

    更新日期:2003-03-18 00:00:00

  • Chloroplasts extend stromules independently and in response to internal redox signals.

    abstract::A fundamental mystery of plant cell biology is the occurrence of "stromules," stroma-filled tubular extensions from plastids (such as chloroplasts) that are universally observed in plants but whose functions are, in effect, completely unknown. One prevalent hypothesis is that stromules exchange signals or metabolites ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1511570112

    authors: Brunkard JO,Runkel AM,Zambryski PC

    更新日期:2015-08-11 00:00:00

  • Neurotensin induces IL-6 secretion in mouse preadipocytes and adipose tissues during 2,4,6,-trinitrobenzensulphonic acid-induced colitis.

    abstract::Mesenteric fat is known to undergo inflammatory changes after 2,4,6,-trinitrobenzensulphonic acid (TNBS)-induced colitis. Neurotensin (NT) and neurotensin receptor 1 (NTR1) have been shown to play a major role in the pathogenesis of intestinal inflammation. This led us to explore whether NT and NTR1 are expressed in t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0903499106

    authors: Koon HW,Kim YS,Xu H,Kumar A,Zhao D,Karagiannides I,Dobner PR,Pothoulakis C

    更新日期:2009-05-26 00:00:00

  • Algal ancestor of land plants was preadapted for symbiosis.

    abstract::Colonization of land by plants was a major transition on Earth, but the developmental and genetic innovations required for this transition remain unknown. Physiological studies and the fossil record strongly suggest that the ability of the first land plants to form symbiotic associations with beneficial fungi was one ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1515426112

    authors: Delaux PM,Radhakrishnan GV,Jayaraman D,Cheema J,Malbreil M,Volkening JD,Sekimoto H,Nishiyama T,Melkonian M,Pokorny L,Rothfels CJ,Sederoff HW,Stevenson DW,Surek B,Zhang Y,Sussman MR,Dunand C,Morris RJ,Roux C,Wong GK

    更新日期:2015-10-27 00:00:00

  • Lysine methyltransferase G9a methylates the transcription factor MyoD and regulates skeletal muscle differentiation.

    abstract::Skeletal muscle cells have served as a paradigm for understanding mechanisms leading to cellular differentiation. The proliferation and differentiation of muscle precursor cells require the concerted activity of myogenic regulatory factors including MyoD. In addition, chromatin modifiers mediate dynamic modifications ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1111628109

    authors: Ling BM,Bharathy N,Chung TK,Kok WK,Li S,Tan YH,Rao VK,Gopinadhan S,Sartorelli V,Walsh MJ,Taneja R

    更新日期:2012-01-17 00:00:00

  • Microinjection of antisense c-mos oligonucleotides prevents meiosis II in the maturing mouse egg.

    abstract::Injection of antisense oligonucleotides was used to investigate the function of c-mos in murine oocytes. Oocytes injected with antisense c-mos oligonucleotides completed the first meiotic division but failed to initiate meiosis II. Instead, loss of c-mos function led to chromosome decondensation, reformation of a nucl...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.86.18.7038

    authors: O'Keefe SJ,Wolfes H,Kiessling AA,Cooper GM

    更新日期:1989-09-01 00:00:00

  • Suppression of an absolute defect in type IV pilus biogenesis by loss-of-function mutations in pilT, a twitching motility gene in Neisseria gonorrhoeae.

    abstract::Type IV pili of Neisseria gonorrhoeae, the Gram-negative etiologic agent of gonorrhea, facilitate colonization of the human host. Gonococcal PilT, a protein belonging to a large family of molecules sharing a highly conserved nucleotide binding domain motif, has been shown to be dispensable for organelle biogenesis but...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.25.14973

    authors: Wolfgang M,Park HS,Hayes SF,van Putten JP,Koomey M

    更新日期:1998-12-08 00:00:00

  • Blastocyst's state of activity determines the "window" of implantation in the receptive mouse uterus.

    abstract::The present investigation studied the influence of the blastocyst's state of activity on the "window" of implantation in the receptive uterus in the mouse. The receptive state of the uterus is defined as the limited time when the uterine milieu is favorable to blastocyst acceptance and implantation. In the mouse, impl...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.21.10159

    authors: Paria BC,Huet-Hudson YM,Dey SK

    更新日期:1993-11-01 00:00:00

  • Shear stress activates mitochondrial oxidative phosphorylation by reducing plasma membrane cholesterol in vascular endothelial cells.

    abstract::Vascular endothelial cells (ECs) sense and respond to hemodynamic shear stress, which is critical for circulatory homeostasis and the pathophysiology of vascular diseases. The mechanisms of shear stress mechanotransduction, however, remain elusive. We previously demonstrated a direct role of mitochondria in the purine...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2014029117

    authors: Yamamoto K,Nogimori Y,Imamura H,Ando J

    更新日期:2020-12-29 00:00:00

  • Cytoplasmic transfer of resistance to antimycin A in Chinese hamster cells.

    abstract::A mutant subline of V79 Chinese hamster cells resistant to antimycin A (ANT) was obtained by treatment with ethyl methanesulfonate followed by serial selection in ANT-containing medium. Clonal derivatives of the resistant line are less susceptible than parent cells to growth inhibition by ANT in mass populations and s...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.75.11.5604

    authors: Harris M

    更新日期:1978-11-01 00:00:00

  • Human methionine synthase reductase is a molecular chaperone for human methionine synthase.

    abstract::Sustained activity of mammalian methionine synthase (MS) requires MS reductase (MSR), but there have been few studies of the interactions between these two proteins. In this study, recombinant human MS (hMS) and MSR (hMSR) were expressed in baculovirus-infected insect cells and purified to homogeneity. hMSR maintained...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0603694103

    authors: Yamada K,Gravel RA,Toraya T,Matthews RG

    更新日期:2006-06-20 00:00:00

  • An accumulator model for spontaneous neural activity prior to self-initiated movement.

    abstract::A gradual buildup of neuronal activity known as the "readiness potential" reliably precedes voluntary self-initiated movements, in the average time locked to movement onset. This buildup is presumed to reflect the final stages of planning and preparation for movement. Here we present a different interpretation of the ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1210467109

    authors: Schurger A,Sitt JD,Dehaene S

    更新日期:2012-10-16 00:00:00

  • Aragonite crystallization in primary cell cultures of multicellular isolates from a hard coral, Pocillopora damicornis.

    abstract::The foundation of marine coral reef ecosystems is calcium carbonate accumulated primarily by the action of hard corals (Coelenterata: Anthozoa: Scleractinia). Colonial hard coral polyps cover the surface of the reef and deposit calcium carbonate as the aragonite polymorph, stabilized into a continuous calcareous skele...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.211439698

    authors: Domart-Coulon IJ,Elbert DC,Scully EP,Calimlim PS,Ostrander GK

    更新日期:2001-10-09 00:00:00

  • The wing of the enhancer-binding domain of Mu phage transposase is flexible and is essential for efficient transposition.

    abstract::A tetramer of the Mu transposase (MuA) pairs the recombination sites, cleaves the donor DNA, and joins these ends to a target DNA by strand transfer. Juxtaposition of the recombination sites is accomplished by the assembly of a stable synaptic complex of MuA protein and Mu DNA. This initial critical step is facilitate...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.93.3.1146

    authors: Clubb RT,Mizuuchi M,Huth JR,Omichinski JG,Savilahti H,Mizuuchi K,Clore GM,Gronenborn AM

    更新日期:1996-02-06 00:00:00

  • Molecular cloning of avian myelocytomatosis virus (MC29) transforming sequences.

    abstract::Avian myelocytomatosis virus (MC29), a defective acute leukemia virus, has a broad oncogenic spectrum in vivo and transforms fibroblasts and hematopoietic target cells in vitro. We have used recombinant DNA technology to isolate and to characterize the sequences that are essential in the transformation process. Integr...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.78.3.1518

    authors: Lautenberger JA,Schulz RA,Garon CF,Tsichlis PN,Papas TS

    更新日期:1981-03-01 00:00:00

  • PII-like signaling protein SbtB links cAMP sensing with cyanobacterial inorganic carbon response.

    abstract::Cyanobacteria are phototrophic prokaryotes that evolved oxygenic photosynthesis ∼2.7 billion y ago and are presently responsible for ∼10% of total global photosynthetic production. To cope with the evolutionary pressure of dropping ambient CO2 concentrations, they evolved a CO2-concentrating mechanism (CCM) to augment...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1803790115

    authors: Selim KA,Haase F,Hartmann MD,Hagemann M,Forchhammer K

    更新日期:2018-05-22 00:00:00

  • Revealing the dual streams of speech processing.

    abstract::Several dual route models of human speech processing have been proposed suggesting a large-scale anatomical division between cortical regions that support motor-phonological aspects vs. lexical-semantic aspects of speech processing. However, to date, there is no complete agreement on what areas subserve each route or ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1614038114

    authors: Fridriksson J,Yourganov G,Bonilha L,Basilakos A,Den Ouden DB,Rorden C

    更新日期:2016-12-27 00:00:00

  • Mice lacking major histocompatibility complex class I and class II molecules.

    abstract::Mice lacking major histocompatibility complex (MHC) antigens were generated by mating beta 2-microglobulin-deficient, and therefore class I-deficient, animals with MHC class II-deficient animals. When housed under sterile conditions, the resulting MHC-deficient mice appear healthy, survive for many months, and breed s...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.9.3913

    authors: Grusby MJ,Auchincloss H Jr,Lee R,Johnson RS,Spencer JP,Zijlstra M,Jaenisch R,Papaioannou VE,Glimcher LH

    更新日期:1993-05-01 00:00:00

  • Antibody biomarker discovery through in vitro directed evolution of consensus recognition epitopes.

    abstract::To enable discovery of serum antibodies indicative of disease and simultaneously develop reagents suitable for diagnosis, in vitro directed evolution was applied to identify consensus peptides recognized by patients' serum antibodies. Bacterial cell-displayed peptide libraries were quantitatively screened for binders ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1314792110

    authors: Ballew JT,Murray JA,Collin P,Mäki M,Kagnoff MF,Kaukinen K,Daugherty PS

    更新日期:2013-11-26 00:00:00

  • Omics-based identification of Arabidopsis Myb transcription factors regulating aliphatic glucosinolate biosynthesis.

    abstract::Understanding plant metabolism as an integrated system is essential for metabolic engineering aimed at the effective production of compounds useful to human life and the global environment. The "omics" approach integrates transcriptome and metabolome data into a single data set and can lead to the identification of un...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0611629104

    authors: Hirai MY,Sugiyama K,Sawada Y,Tohge T,Obayashi T,Suzuki A,Araki R,Sakurai N,Suzuki H,Aoki K,Goda H,Nishizawa OI,Shibata D,Saito K

    更新日期:2007-04-10 00:00:00

  • Engagement of SLAMF3 enhances CD4+ T-cell sensitivity to IL-2 and favors regulatory T-cell polarization in systemic lupus erythematosus.

    abstract::Signaling lymphocytic activation molecule family 3 (SLAMF3/Ly9) is a coregulatory molecule implicated in T-cell activation and differentiation. Systemic lupus erythematosus (SLE) is characterized by aberrant T-cell activation and compromised IL-2 production, leading to abnormal regulatory T-cell (Treg) development/fun...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1605081113

    authors: Comte D,Karampetsou MP,Kis-Toth K,Yoshida N,Bradley SJ,Mizui M,Kono M,Solomon JR,Kyttaris VC,Tsokos GC

    更新日期:2016-08-16 00:00:00

  • Wire-like charge transport at near constant bridge energy through fluorene oligomers.

    abstract::The study of photoinitiated electron transfer in donor-bridge-acceptor molecules has helped elucidate the distance dependence of electron transfer rates and behavior of various electron transfer mechanisms. In all reported cases, the energies of the bridge electronic states involved in the electron transfer change dra...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0408940102

    authors: Goldsmith RH,Sinks LE,Kelley RF,Betzen LJ,Liu W,Weiss EA,Ratner MA,Wasielewski MR

    更新日期:2005-03-08 00:00:00

  • Osteonectin cDNA sequence reveals potential binding regions for calcium and hydroxyapatite and shows homologies with both a basement membrane protein (SPARC) and a serine proteinase inhibitor (ovomucoid).

    abstract::Osteonectin is a prominent noncollagenous protein of developing bone. A 2150-base-pair cDNA coding for osteonectin, isolated from a bovine bone cell lambda gt11 expression library, was sequenced and identified by comparison with protein sequence data. The nucleotide sequence predicts that osteonectin contains 304 amin...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.85.9.2919

    authors: Bolander ME,Young MF,Fisher LW,Yamada Y,Termine JD

    更新日期:1988-05-01 00:00:00

  • Regulation of the in vitro antibody response by neuroendocrine hormones.

    abstract::Treatment of lymphocytes with inducers of interferon alpha (IFN-alpha) results in the production of corticotropin (ACTH) and endorphin-like activities. The pro-opiomelanocortin-derived hormones ACTH and alpha-, beta-, and gamma-endorphin and the structurally related hormones [Leu]- and [Met]enkephalin were therefore t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.79.13.4171

    authors: Johnson HM,Smith EM,Torres BA,Blalock JE

    更新日期:1982-07-01 00:00:00