HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle.


:Cornelia de Lange syndrome (CdLS) is a dominantly inherited congenital malformation disorder, caused by mutations in the cohesin-loading protein NIPBL for nearly 60% of individuals with classical CdLS, and by mutations in the core cohesin components SMC1A (~5%) and SMC3 (<1%) for a smaller fraction of probands. In humans, the multisubunit complex cohesin is made up of SMC1, SMC3, RAD21 and a STAG protein. These form a ring structure that is proposed to encircle sister chromatids to mediate sister chromatid cohesion and also has key roles in gene regulation. SMC3 is acetylated during S-phase to establish cohesiveness of chromatin-loaded cohesin, and in yeast, the class I histone deacetylase Hos1 deacetylates SMC3 during anaphase. Here we identify HDAC8 as the vertebrate SMC3 deacetylase, as well as loss-of-function HDAC8 mutations in six CdLS probands. Loss of HDAC8 activity results in increased SMC3 acetylation and inefficient dissolution of the ‘used’ cohesin complex released from chromatin in both prophase and anaphase. SMC3 with retained acetylation is loaded onto chromatin, and chromatin immunoprecipitation sequencing analysis demonstrates decreased occupancy of cohesin localization sites that results in a consistent pattern of altered transcription seen in CdLS cell lines with either NIPBL or HDAC8 mutations.






Deardorff MA,Bando M,Nakato R,Watrin E,Itoh T,Minamino M,Saitoh K,Komata M,Katou Y,Clark D,Cole KE,De Baere E,Decroos C,Di Donato N,Ernst S,Francey LJ,Gyftodimou Y,Hirashima K,Hullings M,Ishikawa Y,Jaulin C,Kaur




Has Abstract


2012-09-13 00:00:00
















  • Attosecond control of electronic processes by intense light fields.

    abstract::The amplitude and frequency of laser light can be routinely measured and controlled on a femtosecond (10(-15) s) timescale. However, in pulses comprising just a few wave cycles, the amplitude envelope and carrier frequency are not sufficient to characterize and control laser radiation, because evolution of the light f...


    pub_type: 杂志文章


    authors: Baltuska A,Udem T,Uiberacker M,Hentschel M,Goulielmakis E,Gohle Ch,Holzwarth R,Yakovlev VS,Scrinzi A,Hänsch TW,Krausz F

    更新日期:2003-02-06 00:00:00

  • Retinoblastoma-protein-dependent cell-cycle inhibition by the tumour suppressor p16.

    abstract::D-type cyclins, in association with the cyclin-dependent kinases Cdk4 or Cdk6, promote progression through the G1 phase of the cell cycle by phosphorylating the retinoblastoma protein (RB). The activities of Cdk4 and Cdk6 are constrained by inhibitors such as p16, the product of the CDKN2 gene on human chromosome 9p21...


    pub_type: 杂志文章


    authors: Lukas J,Parry D,Aagaard L,Mann DJ,Bartkova J,Strauss M,Peters G,Bartek J

    更新日期:1995-06-08 00:00:00

  • Signature of optimal doping in Hall-effect measurements on a high-temperature superconductor.

    abstract::High-temperature superconductivity is achieved by doping copper oxide insulators with charge carriers. The density of carriers in conducting materials can be determined from measurements of the Hall voltage--the voltage transverse to the flow of the electrical current that is proportional to an applied magnetic field....


    pub_type: 杂志文章


    authors: Balakirev FF,Betts JB,Migliori A,Ono S,Ando Y,Boebinger GS

    更新日期:2003-08-21 00:00:00

  • Retinoid X receptor is an auxiliary protein for thyroid hormone and retinoic acid receptors.

    abstract::Thyroid hormones and retinoic acid function through nuclear receptors that belong to the steroid/thyroid-hormone receptor superfamily. Thyroid hormone receptors (TRs) and retinoic acid receptors (RARs) require auxiliary nuclear proteins for efficient DNA binding. Here we report that retinoid X receptors RXR alpha is o...


    pub_type: 杂志文章


    authors: Zhang XK,Hoffmann B,Tran PB,Graupner G,Pfahl M

    更新日期:1992-01-30 00:00:00

  • Chemical rescue of cleft palate and midline defects in conditional GSK-3beta mice.

    abstract::Glycogen synthase kinase-3beta (GSK-3beta) has integral roles in a variety of biological processes, including development, diabetes, and the progression of Alzheimer's disease. As such, a thorough understanding of GSK-3beta function will have a broad impact on human biology and therapeutics. Because GSK-3beta interact...


    pub_type: 杂志文章


    authors: Liu KJ,Arron JR,Stankunas K,Crabtree GR,Longaker MT

    更新日期:2007-03-01 00:00:00

  • Evolution of ageing.

    abstract::An evolutionary view of ageing suggests that mortality may be due to an energy-saving strategy of reduced error regulation in somatic cells. This supports Orgel's 'error catastrophe' hypothesis and offers a new basis for the study of normal and abnormal ageing syndromes and of apparently immortal transformed cell line...


    pub_type: 杂志文章


    authors: Kirkwood TB

    更新日期:1977-11-24 00:00:00

  • Measurement of a confinement induced neutron phase.

    abstract::Particle physicists see neutrons as tiny massive particles with a confinement radius of about 0.7 fm and a distinct internal quark gluon structure. In quantum mechanics, neutrons are described by wave packets whose spatial extent may become ten orders of magnitude larger than the confinement radius, and can even reach...


    pub_type: 杂志文章


    authors: Rauch H,Lemmel H,Baron M,Loidl R

    更新日期:2002-06-06 00:00:00

  • CDK8 is a colorectal cancer oncogene that regulates beta-catenin activity.

    abstract::Aberrant activation of the canonical WNT/beta-catenin pathway occurs in almost all colorectal cancers and contributes to their growth, invasion and survival. Although dysregulated beta-catenin activity drives colon tumorigenesis, further genetic perturbations are required to elaborate full malignant transformation. To...


    pub_type: 杂志文章


    authors: Firestein R,Bass AJ,Kim SY,Dunn IF,Silver SJ,Guney I,Freed E,Ligon AH,Vena N,Ogino S,Chheda MG,Tamayo P,Finn S,Shrestha Y,Boehm JS,Jain S,Bojarski E,Mermel C,Barretina J,Chan JA,Baselga J,Tabernero J,Root DE,

    更新日期:2008-09-25 00:00:00

  • Sequence and analysis of chromosome 2 of Dictyostelium discoideum.

    abstract::The genome of the lower eukaryote Dictyostelium discoideum comprises six chromosomes. Here we report the sequence of the largest, chromosome 2, which at 8 megabases (Mb) represents about 25% of the genome. Despite an A + T content of nearly 80%, the chromosome codes for 2,799 predicted protein coding genes and 73 tran...


    pub_type: 杂志文章


    authors: Glöckner G,Eichinger L,Szafranski K,Pachebat JA,Bankier AT,Dear PH,Lehmann R,Baumgart C,Parra G,Abril JF,Guigó R,Kumpf K,Tunggal B,Cox E,Quail MA,Platzer M,Rosenthal A,Noegel AA,Dictyostelium Genome Sequencing Consort

    更新日期:2002-07-04 00:00:00

  • Coupled dynamics of body mass and population growth in response to environmental change.

    abstract::Environmental change has altered the phenology, morphological traits and population dynamics of many species. However, the links underlying these joint responses remain largely unknown owing to a paucity of long-term data and the lack of an appropriate analytical framework. Here we investigate the link between phenoty...


    pub_type: 杂志文章


    authors: Ozgul A,Childs DZ,Oli MK,Armitage KB,Blumstein DT,Olson LE,Tuljapurkar S,Coulson T

    更新日期:2010-07-22 00:00:00

  • Modern freshwater microbialite analogues for ancient dendritic reef structures.

    abstract::Microbialites are organosedimentary structures that can be constructed by a variety of metabolically distinct taxa. Consequently, microbialite structures abound in the fossil record, although the exact nature of the biogeochemical processes that produced them is often unknown. One such class of ancient calcareous stru...


    pub_type: 杂志文章


    authors: Laval B,Cady SL,Pollack JC,McKay CP,Bird JS,Grotzinger JP,Ford DC,Bohm HR

    更新日期:2000-10-05 00:00:00

  • Sirtuin activators mimic caloric restriction and delay ageing in metazoans.

    abstract::Caloric restriction extends lifespan in numerous species. In the budding yeast Saccharomyces cerevisiae this effect requires Sir2 (ref. 1), a member of the sirtuin family of NAD+-dependent deacetylases. Sirtuin activating compounds (STACs) can promote the survival of human cells and extend the replicative lifespan of ...


    pub_type: 杂志文章


    authors: Wood JG,Rogina B,Lavu S,Howitz K,Helfand SL,Tatar M,Sinclair D

    更新日期:2004-08-05 00:00:00

  • Solvation energy in protein folding and binding.

    abstract::We have developed a method for calculating the stability in water of protein structures, starting from their atomic coordinates. The contribution of each protein atom to the solvation free energy is estimated as the product of the accessibility of the atom to solvent and its atomic solvation parameter. Applications of...


    pub_type: 杂志文章


    authors: Eisenberg D,McLachlan AD

    更新日期:1986-01-16 00:00:00

  • The interaction landscape between transcription factors and the nucleosome.

    abstract::Nucleosomes cover most of the genome and are thought to be displaced by transcription factors in regions that direct gene expression. However, the modes of interaction between transcription factors and nucleosomal DNA remain largely unknown. Here we systematically explore interactions between the nucleosome and 220 tr...


    pub_type: 杂志文章


    authors: Zhu F,Farnung L,Kaasinen E,Sahu B,Yin Y,Wei B,Dodonova SO,Nitta KR,Morgunova E,Taipale M,Cramer P,Taipale J

    更新日期:2018-10-01 00:00:00

  • Neuropeptide Y functions as a neuroproliferative factor.

    abstract::Neuropeptide Y (NPY) has a number of functions in mammalian physiology. Here we identify a role for NPY in promoting proliferation of postnatal neuronal precursor cells. NPY is synthesized in the postnatal olfactory epithelium by sustentacular cells, previously proposed to function only in structural support. Mice wit...


    pub_type: 杂志文章


    authors: Hansel DE,Eipper BA,Ronnett GV

    更新日期:2001-04-19 00:00:00

  • Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide.

    abstract::Plasmacytoid dendritic cells (pDCs) sense viral and microbial DNA through endosomal Toll-like receptors to produce type 1 interferons. pDCs do not normally respond to self-DNA, but this restriction seems to break down in human autoimmune disease by an as yet poorly understood mechanism. Here we identify the antimicrob...


    pub_type: 杂志文章


    authors: Lande R,Gregorio J,Facchinetti V,Chatterjee B,Wang YH,Homey B,Cao W,Wang YH,Su B,Nestle FO,Zal T,Mellman I,Schröder JM,Liu YJ,Gilliet M

    更新日期:2007-10-04 00:00:00

  • Structure of the cro repressor from bacteriophage lambda and its interaction with DNA.

    abstract::The three-dimensional structure of the 66-amino acid cro repressor protein of bacteriophage lambda suggests how it binds to its operator DNA. We propose that a dimer of cro protein is bound to the B-form of DNA with the 2-fold axis of the dimer coincident with the 2-fold axis of DNA. A pair of 2-fold-related alpha-hel...


    pub_type: 杂志文章


    authors: Anderson WF,Ohlendorf DH,Takeda Y,Matthews BW

    更新日期:1981-04-30 00:00:00

  • Radial optic flow induces vergence eye movements with ultra-short latencies.

    abstract::An observer moving forwards through the environment experiences a radial pattern of image motion on each retina. Such patterns of optic flow are a potential source of information about the observer's rate of progress, direction of heading and time to reach objects that lie ahead. As the viewing distance changes there ...


    pub_type: 杂志文章


    authors: Busettini C,Masson GS,Miles FA

    更新日期:1997-12-04 00:00:00

  • A carbon isotope challenge to the snowball Earth.

    abstract::The snowball Earth hypothesis postulates that the planet was entirely covered by ice for millions of years in the Neoproterozoic era, in a self-enhanced glaciation caused by the high albedo of the ice-covered planet. In a hard-snowball picture, the subsequent rapid unfreezing resulted from an ultra-greenhouse event at...


    pub_type: 杂志文章


    authors: Sansjofre P,Ader M,Trindade RI,Elie M,Lyons J,Cartigny P,Nogueira AC

    更新日期:2011-10-05 00:00:00

  • Structure of the T4 baseplate and its function in triggering sheath contraction.

    abstract::Several systems, including contractile tail bacteriophages, the type VI secretion system and R-type pyocins, use a multiprotein tubular apparatus to attach to and penetrate host cell membranes. This macromolecular machine resembles a stretched, coiled spring (or sheath) wound around a rigid tube with a spike-shaped pr...


    pub_type: 杂志文章


    authors: Taylor NM,Prokhorov NS,Guerrero-Ferreira RC,Shneider MM,Browning C,Goldie KN,Stahlberg H,Leiman PG

    更新日期:2016-05-19 00:00:00

  • Subsecond dopamine release promotes cocaine seeking.

    abstract::The dopamine-containing projection from the ventral tegmental area of the midbrain to the nucleus accumbens is critically involved in mediating the reinforcing properties of cocaine. Although neurons in this area respond to rewards on a subsecond timescale, neurochemical studies have only addressed the role of dopamin...


    pub_type: 杂志文章


    authors: Phillips PE,Stuber GD,Heien ML,Wightman RM,Carelli RM

    更新日期:2003-04-10 00:00:00

  • Two-million-year-old snapshots of atmospheric gases from Antarctic ice.

    abstract::Over the past eight hundred thousand years, glacial-interglacial cycles oscillated with a period of one hundred thousand years ('100k world'1). Ice core and ocean sediment data have shown that atmospheric carbon dioxide, Antarctic temperature, deep ocean temperature, and global ice volume correlated strongly with each...


    pub_type: 杂志文章


    authors: Yan Y,Bender ML,Brook EJ,Clifford HM,Kemeny PC,Kurbatov AV,Mackay S,Mayewski PA,Ng J,Severinghaus JP,Higgins JA

    更新日期:2019-10-01 00:00:00

  • Learning-related feedforward inhibitory connectivity growth required for memory precision.

    abstract::In the adult brain, new synapses are formed and pre-existing ones are lost, but the function of this structural plasticity has remained unclear. Learning of new skills is correlated with formation of new synapses. These may directly encode new memories, but they may also have more general roles in memory encoding and ...


    pub_type: 杂志文章


    authors: Ruediger S,Vittori C,Bednarek E,Genoud C,Strata P,Sacchetti B,Caroni P

    更新日期:2011-05-26 00:00:00

  • Antero-posterior tissue polarity links mesoderm convergent extension to axial patterning.

    abstract::Remodelling its shape, or morphogenesis, is a fundamental property of living tissue. It underlies much of embryonic development and numerous pathologies. Convergent extension (CE) of the axial mesoderm of vertebrates is an intensively studied model for morphogenetic processes that rely on cell rearrangement. It involv...


    pub_type: 杂志文章


    authors: Ninomiya H,Elinson RP,Winklbauer R

    更新日期:2004-07-15 00:00:00

  • A proteasomal ATPase subunit recognizes the polyubiquitin degradation signal.

    abstract::The 26S proteasome is the chief site of regulatory protein turnover in eukaryotic cells. It comprises one 20S catalytic complex (composed of four stacked rings of seven members) and two axially positioned 19S regulatory complexes (each containing about 18 subunits) that control substrate access to the catalytic chambe...


    pub_type: 杂志文章


    authors: Lam YA,Lawson TG,Velayutham M,Zweier JL,Pickart CM

    更新日期:2002-04-18 00:00:00

  • The contribution of bone to whole-organism physiology.

    abstract::The mouse genetic revolution has shown repeatedly that most organs have more functions than expected. This has led to the realization that, in addition to a molecular and cellular approach, there is a need for a whole-organism study of physiology. The skeleton is an example of how a whole-organism approach to physiolo...


    pub_type: 杂志文章,评审


    authors: Karsenty G,Ferron M

    更新日期:2012-01-18 00:00:00

  • Implications of early hominid labyrinthine morphology for evolution of human bipedal locomotion.

    abstract::The upright posture and obligatory bipedalism of modern humans are unique among living primates. The evolutionary history of this behaviour has traditionally been pursued by functional analysis of the postcranial skeleton and the preserved footprint trails of fossil hominids. Here we report a systematic attempt to rec...


    pub_type: 杂志文章


    authors: Spoor F,Wood B,Zonneveld F

    更新日期:1994-06-23 00:00:00

  • Guard cell abscisic acid signalling and engineering drought hardiness in plants.

    abstract::Guard cells are located in the epidermis of plant leaves, and in pairs surround stomatal pores. These control both the influx of CO2 as a raw material for photosynthesis and water loss from plants through transpiration to the atmosphere. Guard cells have become a highly developed system for dissecting early signal tra...


    pub_type: 杂志文章,评审


    authors: Schroeder JI,Kwak JM,Allen GJ

    更新日期:2001-03-15 00:00:00

  • Experience leaves a lasting structural trace in cortical circuits.

    abstract::Sensory experiences exert a powerful influence on the function and future performance of neuronal circuits in the mammalian neocortex. Restructuring of synaptic connections is believed to be one mechanism by which cortical circuits store information about the sensory world. Excitatory synaptic structures, such as dend...


    pub_type: 杂志文章


    authors: Hofer SB,Mrsic-Flogel TD,Bonhoeffer T,Hübener M

    更新日期:2009-01-15 00:00:00

  • Mutations of two PMS homologues in hereditary nonpolyposis colon cancer.

    abstract::Hereditary nonpolyposis colorectal cancer (HNPCC) is one of man's commonest hereditary diseases. Several studies have implicated a defect in DNA mismatch repair in the pathogenesis of this disease. In particular, hMSH2 and hMLH1 homologues of the bacterial DNA mismatch repair genes mutS and mutL, respectively, were sh...


    pub_type: 杂志文章


    authors: Nicolaides NC,Papadopoulos N,Liu B,Wei YF,Carter KC,Ruben SM,Rosen CA,Haseltine WA,Fleischmann RD,Fraser CM

    更新日期:1994-09-01 00:00:00