Citrullination-acetylation interplay guides E2F-1 activity during the inflammatory response.

Abstract:

:Peptidyl arginine deiminase 4 (PAD4) is a nuclear enzyme that converts arginine residues to citrulline. Although increasingly implicated in inflammatory disease and cancer, the mechanism of action of PAD4 and its functionally relevant pathways remains unclear. E2F transcription factors are a family of master regulators that coordinate gene expression during cellular proliferation and diverse cell fates. We show that E2F-1 is citrullinated by PAD4 in inflammatory cells. Citrullination of E2F-1 assists its chromatin association, specifically to cytokine genes in granulocyte cells. Mechanistically, citrullination augments binding of the BET (bromodomain and extra-terminal domain) family bromodomain reader BRD4 (bromodomain-containing protein 4) to an acetylated domain in E2F-1, and PAD4 and BRD4 coexist with E2F-1 on cytokine gene promoters. Accordingly, the combined inhibition of PAD4 and BRD4 disrupts the chromatin-bound complex and suppresses cytokine gene expression. In the murine collagen-induced arthritis model, chromatin-bound E2F-1 in inflammatory cells and consequent cytokine expression are diminished upon small-molecule inhibition of PAD4 and BRD4, and the combined treatment is clinically efficacious in preventing disease progression. Our results shed light on a new transcription-based mechanism that mediates the inflammatory effect of PAD4 and establish the interplay between citrullination and acetylation in the control of E2F-1 as a regulatory interface for driving inflammatory gene expression.

journal_name

Sci Adv

journal_title

Science advances

authors

Ghari F,Quirke AM,Munro S,Kawalkowska J,Picaud S,McGouran J,Subramanian V,Muth A,Williams R,Kessler B,Thompson PR,Fillipakopoulos P,Knapp S,Venables PJ,La Thangue NB

doi

10.1126/sciadv.1501257

subject

Has Abstract

pub_date

2016-02-05 00:00:00

pages

e1501257

issue

2

issn

2375-2548

pii

1501257

journal_volume

2

pub_type

杂志文章
  • Saigas on the brink: Multidisciplinary analysis of the factors influencing mass mortality events.

    abstract::In 2015, more than 200,000 saiga antelopes died in 3 weeks in central Kazakhstan. The proximate cause of death is confirmed as hemorrhagic septicemia caused by the bacterium Pasteurella multocida type B, based on multiple strands of evidence. Statistical modeling suggests that there was unusually high relative humidit...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aao2314

    authors: Kock RA,Orynbayev M,Robinson S,Zuther S,Singh NJ,Beauvais W,Morgan ER,Kerimbayev A,Khomenko S,Martineau HM,Rystaeva R,Omarova Z,Wolfs S,Hawotte F,Radoux J,Milner-Gulland EJ

    更新日期:2018-01-17 00:00:00

  • Allosteric modulation of nucleoporin assemblies by intrinsically disordered regions.

    abstract::Intrinsically disordered regions (IDRs) of proteins are implicated in key macromolecular interactions. However, the molecular forces underlying IDR function within multicomponent assemblies remain elusive. By combining thermodynamic and structural data, we have discovered an allostery-based mechanism regulating the so...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aax1836

    authors: Blus BJ,Koh J,Krolak A,Seo HS,Coutavas E,Blobel G

    更新日期:2019-11-27 00:00:00

  • Direct quantitative measurement of the C═O⋅⋅⋅H-C bond by atomic force microscopy.

    abstract::The hydrogen atom-the smallest and most abundant atom-is of utmost importance in physics and chemistry. Although many analysis methods have been applied to its study, direct observation of hydrogen atoms in a single molecule remains largely unexplored. We use atomic force microscopy (AFM) to resolve the outermost hydr...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.1603258

    authors: Kawai S,Nishiuchi T,Kodama T,Spijker P,Pawlak R,Meier T,Tracey J,Kubo T,Meyer E,Foster AS

    更新日期:2017-05-12 00:00:00

  • Bcl11b prevents fatal autoimmunity by promoting Treg cell program and constraining innate lineages in Treg cells.

    abstract::Regulatory T (Treg) cells are essential for peripheral tolerance and rely on the transcription factor (TF) Foxp3 for their generation and function. Several other TFs are critical for the Treg cell program. We found that mice deficient in Bcl11b TF solely in Treg cells developed fatal autoimmunity, and Bcl11b-deficient...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aaw0480

    authors: Drashansky TT,Helm E,Huo Z,Curkovic N,Kumar P,Luo X,Parthasarathy U,Zuniga A,Cho JJ,Lorentsen KJ,Xu Z,Uddin M,Moshkani S,Zhou L,Avram D

    更新日期:2019-08-07 00:00:00

  • Ferroelectric self-assembled molecular materials showing both rectifying and switchable conductivity.

    abstract::Advanced molecular materials that combine two or more physical properties are typically constructed by combining different molecules, each being responsible for one of the properties required. Ideally, single molecules could take care of this combined functionality, provided they are self-assembled correctly and endow...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.1701017

    authors: Gorbunov AV,Garcia Iglesias M,Guilleme J,Cornelissen TD,Roelofs WSC,Torres T,González-Rodríguez D,Meijer EW,Kemerink M

    更新日期:2017-09-29 00:00:00

  • Bioinspired shape-memory graphene film with tunable wettability.

    abstract::Functional materials with specific surface wettability play an important role in a wide variety of areas. Inspired by nature's Nepenthes pitcher plant, we present a novel slippery film with tunable wettability based on a shape-memory graphene sponge. The porous graphene sponge coated with shape-memory polymer was used...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.1700004

    authors: Wang J,Sun L,Zou M,Gao W,Liu C,Shang L,Gu Z,Zhao Y

    更新日期:2017-06-02 00:00:00

  • Observation of inverse Edelstein effect in Rashba-split 2DEG between SrTiO3 and LaAlO3 at room temperature.

    abstract::The Rashba physics has been intensively studied in the field of spin orbitronics for the purpose of searching novel physical properties and the ferromagnetic (FM) magnetization switching for technological applications. We report our observation of the inverse Edelstein effect up to room temperature in the Rashba-split...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.1602312

    authors: Song Q,Zhang H,Su T,Yuan W,Chen Y,Xing W,Shi J,Sun J,Han W

    更新日期:2017-03-17 00:00:00

  • Tip-enhanced ablation and ionization mass spectrometry for nanoscale chemical analysis.

    abstract::Spectroscopic methods with nanoscale lateral resolution are becoming essential in the fields of physics, chemistry, geology, biology, and materials science. However, the lateral resolution of laser-based mass spectrometry imaging (MSI) techniques has so far been limited to the microscale. This report presents the deve...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aaq1059

    authors: Liang Z,Zhang S,Li X,Wang T,Huang Y,Hang W,Yang Z,Li J,Tian Z

    更新日期:2017-12-08 00:00:00

  • Twist again: Dynamically and reversibly controllable chirality in liquid crystalline elastomer microposts.

    abstract::Photoresponsive liquid crystalline elastomers (LCEs) constitute ideal actuators for soft robots because their light-induced macroscopic shape changes can be harnessed to perform specific articulated motions. Conventional LCEs, however, do not typically exhibit complex modes of bending and twisting necessary to perform...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aay5349

    authors: Waters JT,Li S,Yao Y,Lerch MM,Aizenberg M,Aizenberg J,Balazs AC

    更新日期:2020-03-27 00:00:00

  • Impact of complex topology of porous media on phase separation of binary mixtures.

    abstract::Porous materials, which are characterized by the large surface area and percolated nature crucial for transport, play an important role in many technological applications including battery, ion exchange, catalysis, microelectronics, medical diagnosis, and oil recovery. Phase separation of a mixture in such a porous st...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aap9570

    authors: Shimizu R,Tanaka H

    更新日期:2017-12-22 00:00:00

  • Combining scaling relationships overcomes rate versus overpotential trade-offs in O2 molecular electrocatalysis.

    abstract::The development of advanced chemical-to-electrical energy conversions requires fast and efficient electrocatalysis of multielectron/multiproton reactions, such as the oxygen reduction reaction (ORR). Using molecular catalysts, correlations between the reaction rate and energy efficiency have recently been identified. ...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aaz3318

    authors: Martin DJ,Mercado BQ,Mayer JM

    更新日期:2020-03-13 00:00:00

  • Neutrophil extracellular traps exacerbate neurological deficits after traumatic brain injury.

    abstract::Traumatic brain injury (TBI) is a major cause of mortality and morbidity. Preventative measures reduce injury incidence and/or severity, yet one-third of hospitalized patients with TBI die from secondary pathological processes that develop during supervised care. Neutrophils, which orchestrate innate immune responses,...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aax8847

    authors: Vaibhav K,Braun M,Alverson K,Khodadadi H,Kutiyanawalla A,Ward A,Banerjee C,Sparks T,Malik A,Rashid MH,Khan MB,Waters MF,Hess DC,Arbab AS,Vender JR,Hoda N,Baban B,Dhandapani KM

    更新日期:2020-05-29 00:00:00

  • Super-resolution nanoscopy by coherent control on nanoparticle emission.

    abstract::Super-resolution nanoscopy based on wide-field microscopic imaging provided high efficiency but limited resolution. Here, we demonstrate a general strategy to push its resolution down to ~50 nm, which is close to the range of single molecular localization microscopy, without sacrificing the wide-field imaging advantag...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aaw6579

    authors: Liu C,Liu W,Wang S,Li H,Lv Z,Zhang F,Zhang D,Teng J,Zheng T,Li D,Zhang M,Xu P,Gong Q

    更新日期:2020-04-17 00:00:00

  • Nonadiabatic exciton-phonon coupling in Raman spectroscopy of layered materials.

    abstract::We present an ab initio computational approach for the calculation of resonant Raman intensities, including both excitonic and nonadiabatic effects. Our diagrammatic approach, which we apply to two prototype, semiconducting layered materials, allows a detailed analysis of the impact of phonon-mediated exciton-exciton ...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.abb5915

    authors: Reichardt S,Wirtz L

    更新日期:2020-08-07 00:00:00

  • cGAS suppresses genomic instability as a decelerator of replication forks.

    abstract::The cyclic GMP-AMP synthase (cGAS), a sensor of cytosolic DNA, is critical for the innate immune response. Here, we show that loss of cGAS in untransformed and cancer cells results in uncontrolled DNA replication, hyperproliferation, and genomic instability. While the majority of cGAS is cytoplasmic, a fraction of cGA...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.abb8941

    authors: Chen H,Chen H,Zhang J,Wang Y,Simoneau A,Yang H,Levine AS,Zou L,Chen Z,Lan L

    更新日期:2020-10-14 00:00:00

  • Optical computed tomography for spatially isotropic four-dimensional imaging of live single cells.

    abstract::Quantitative three-dimensional (3D) computed tomography (CT) imaging of living single cells enables orientation-independent morphometric analysis of the intricacies of cellular physiology. Since its invention, x-ray CT has become indispensable in the clinic for diagnostic and prognostic purposes due to its quantitativ...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.1602580

    authors: Kelbauskas L,Shetty R,Cao B,Wang KC,Smith D,Wang H,Chao SH,Gangaraju S,Ashcroft B,Kritzer M,Glenn H,Johnson RH,Meldrum DR

    更新日期:2017-12-06 00:00:00

  • Strong coupling of single quantum dots with low-refractive-index/high-refractive-index materials at room temperature.

    abstract::Strong coupling between a cavity and transition dipole moments in emitters leads to vacuum Rabi splitting. Researchers have not reported strong coupling between a single emitter and a dielectric cavity at room temperature until now. In this study, we investigated the photoluminescence (PL) spectra of colloidal quantum...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.abb3095

    authors: Xu X,Jin S

    更新日期:2020-11-20 00:00:00

  • Blue whales (Balaenoptera musculus) optimize foraging efficiency by balancing oxygen use and energy gain as a function of prey density.

    abstract::Terrestrial predators can modulate the energy used for prey capture to maximize efficiency, but diving animals face the conflicting metabolic demands of energy intake and the minimization of oxygen depletion during a breath hold. It is thought that diving predators optimize their foraging success when oxygen use and e...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.1500469

    authors: Hazen EL,Friedlaender AS,Goldbogen JA

    更新日期:2015-10-02 00:00:00

  • Rapid and inefficient kinetics of sickle hemoglobin fiber growth.

    abstract::In sickle cell disease, the aberrant assembly of hemoglobin fibers induces changes in red blood cell morphology and stiffness, which leads to downstream symptoms of the disease. Therefore, understanding of this assembly process will be important for the treatment of sickle cell disease. By performing the highest spati...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aau1086

    authors: Castle BT,Odde DJ,Wood DK

    更新日期:2019-03-13 00:00:00

  • A stratospheric pathway linking a colder Siberia to Barents-Kara Sea sea ice loss.

    abstract::Previous studies have extensively investigated the impact of Arctic sea ice anomalies on the midlatitude circulation and associated surface climate in winter. However, there is an ongoing scientific debate regarding whether and how sea ice retreat results in the observed cold anomaly over the adjacent continents. We p...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aat6025

    authors: Zhang P,Wu Y,Simpson IR,Smith KL,Zhang X,De B,Callaghan P

    更新日期:2018-07-25 00:00:00

  • Paramagnon drag in high thermoelectric figure of merit Li-doped MnTe.

    abstract::Local thermal magnetization fluctuations in Li-doped MnTe are found to increase its thermopower α strongly at temperatures up to 900 K. Below the Néel temperature (TN ~ 307 K), MnTe is antiferromagnetic, and magnon drag contributes αmd to the thermopower, which scales as ~T3. Magnon drag persists into the paramagnetic...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aat9461

    authors: Zheng Y,Lu T,Polash MMH,Rasoulianboroujeni M,Liu N,Manley ME,Deng Y,Sun PJ,Chen XL,Hermann RP,Vashaee D,Heremans JP,Zhao H

    更新日期:2019-09-13 00:00:00

  • Structural basis of sterol recognition by human hedgehog receptor PTCH1.

    abstract::Hedgehog signaling is central in embryonic development and tissue regeneration. Disruption of the pathway is linked to genetic diseases and cancer. Binding of the secreted ligand, Sonic hedgehog (ShhN) to its receptor Patched (PTCH1) activates the signaling pathway. Here, we describe a 3.4-Å cryo-EM structure of the h...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aaw6490

    authors: Qi C,Di Minin G,Vercellino I,Wutz A,Korkhov VM

    更新日期:2019-09-18 00:00:00

  • Intraoceanic subduction spanned the Pacific in the Late Cretaceous-Paleocene.

    abstract::The notorious ~60° bend separating the Hawaiian and Emperor chains marked a prominent change in the motion of the Pacific plate at ~47 Ma (million years ago), but the origin of that change remains an outstanding controversy that bears on the nature of major plate reorganizations. Lesser known but equally significant i...

    journal_title:Science advances

    pub_type: 历史文章,杂志文章

    doi:10.1126/sciadv.aao2303

    authors: Domeier M,Shephard GE,Jakob J,Gaina C,Doubrovine PV,Torsvik TH

    更新日期:2017-11-08 00:00:00

  • Interferon-γ signaling in human iPSC-derived neurons recapitulates neurodevelopmental disorder phenotypes.

    abstract::Maternal immune activation increases the risk of neurodevelopmental disorders. Elevated cytokines, such as interferon-γ (IFN-γ), in offspring's brains play a central role. IFN-γ activates an antiviral cellular state, limiting viral entry and replication. Moreover, IFN-γ is implicated in brain development. We tested th...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aay9506

    authors: Warre-Cornish K,Perfect L,Nagy R,Duarte RRR,Reid MJ,Raval P,Mueller A,Evans AL,Couch A,Ghevaert C,McAlonan G,Loth E,Murphy D,Powell TR,Vernon AC,Srivastava DP,Price J

    更新日期:2020-08-19 00:00:00

  • ERK phosphorylates chromosomal axis component HORMA domain protein HTP-1 to regulate oocyte numbers.

    abstract::Oocyte numbers, a critical determinant of female reproductive fitness, are highly regulated, yet the mechanisms underlying this regulation remain largely undefined. In the Caenorhabditis elegans gonad, RAS/extracellular signal-regulated kinase (ERK) signaling regulates oocyte numbers; mechanisms are unknown. We show t...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.abc5580

    authors: Das D,Chen SY,Arur S

    更新日期:2020-10-30 00:00:00

  • No evidence for DNA N 6-methyladenine in mammals.

    abstract::N6-methyladenine (6mdA) is a widespread DNA modification in bacteria. More recently, 6mdA has also been characterized in mammalian DNA. However, measurements of 6mdA abundance and profiles are often very dissimilar between studies, even when performed on DNA from identical mammalian cell types. Using comprehensive bio...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aay3335

    authors: Douvlataniotis K,Bensberg M,Lentini A,Gylemo B,Nestor CE

    更新日期:2020-03-18 00:00:00

  • Phosphoregulation of Rad51/Rad52 by CDK1 functions as a molecular switch for cell cycle-specific activation of homologous recombination.

    abstract::Homologous recombination is exquisitely activated only during specific cell phases. In the G1 phase, homologous recombination activity is completely suppressed. According to previous reports, the activation of homologous recombination during specific cell phases depends on the kinase activity of cyclin-dependent kinas...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aay2669

    authors: Lim G,Chang Y,Huh WK

    更新日期:2020-02-07 00:00:00

  • Specific ion effects directed noble metal aerogels: Versatile manipulation for electrocatalysis and beyond.

    abstract::Noble metal foams (NMFs) are a new class of functional materials featuring properties of both noble metals and monolithic porous materials, providing impressive prospects in diverse fields. Among reported synthetic methods, the sol-gel approach manifests overwhelming advantages for versatile synthesis of nanostructure...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aaw4590

    authors: Du R,Hu Y,Hübner R,Joswig JO,Fan X,Schneider K,Eychmüller A

    更新日期:2019-05-24 00:00:00

  • A comprehensive portrait of the venom of the giant red bull ant, Myrmecia gulosa, reveals a hyperdiverse hymenopteran toxin gene family.

    abstract::Ants (Hymenoptera: Formicidae) are diverse and ubiquitous, and their ability to sting is familiar to many of us. However, their venoms remain largely unstudied. We provide the first comprehensive characterization of a polypeptidic ant venom, that of the giant red bull ant, Myrmecia gulosa. We reveal a suite of novel p...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aau4640

    authors: Robinson SD,Mueller A,Clayton D,Starobova H,Hamilton BR,Payne RJ,Vetter I,King GF,Undheim EAB

    更新日期:2018-09-12 00:00:00

  • A conserved ATP- and Scc2/4-dependent activity for cohesin in tethering DNA molecules.

    abstract::Sister chromatid cohesion requires cohesin to act as a protein linker to hold chromatids together. How cohesin tethers chromatids remains poorly understood. We have used optical tweezers to visualize cohesin as it holds DNA molecules. We show that cohesin complexes tether DNAs in the presence of Scc2/Scc4 and ATP demo...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aay6804

    authors: Gutierrez-Escribano P,Newton MD,Llauró A,Huber J,Tanasie L,Davy J,Aly I,Aramayo R,Montoya A,Kramer H,Stigler J,Rueda DS,Aragon L

    更新日期:2019-11-27 00:00:00