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  • 1
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    KDM4C (GASC1) lysine demethylase is associated with mitotic chromatin and regulates chromosome segregation during mitosis (2014)
    Oxford University Press
    Details
    Publication Date: 2014-06-03
    Description: Various types of human cancers exhibit amplification or deletion of KDM4A-D members, which selectively demethylate H3K9 and H3K36, thus implicating their activity in promoting carcinogenesis. On this basis, it was hypothesized that dysregulated expression of KDM4A-D family promotes chromosomal instabilities by largely unknown mechanisms. Here, we show that unlike KDM4A-B, KDM4C is associated with chromatin during mitosis. This association is accompanied by a decrease in the mitotic levels of H3K9me3. We also show that the C-terminal region, containing the Tudor domains of KDM4C, is essential for its association with mitotic chromatin. More specifically, we show that R919 residue on the proximal Tudor domain of KDM4C is critical for its association with chromatin during mitosis. Interestingly, we demonstrate that depletion or overexpression of KDM4C, but not KDM4B, leads to over 3-fold increase in the frequency of abnormal mitotic cells showing either misaligned chromosomes at metaphase, anaphase–telophase lagging chromosomes or anaphase–telophase bridges. Furthermore, overexpression of KDM4C demethylase-dead mutant has no detectable effect on mitotic chromosome segregation. Altogether, our findings implicate KDM4C demethylase activity in regulating the fidelity of mitotic chromosome segregation by a yet unknown mechanism.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 2
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    Establishment and maintenance of a heterochromatin domain (2002)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2002-09-07
    Description: The higher-order assembly of chromatin imposes structural organization on the genetic information of eukaryotes and is thought to be largely determined by posttranslational modification of histone tails. Here, we study a 20-kilobase silent domain at the mating-type region of fission yeast as a model for heterochromatin formation. We find that, although histone H3 methylated at lysine 9 (H3 Lys9) directly recruits heterochromatin protein Swi6/HP1, the critical determinant for H3 Lys9 methylation to spread in cis and to be inherited through mitosis and meiosis is Swi6 itself. We demonstrate that a centromere-homologous repeat (cenH) present at the silent mating-type region is sufficient for heterochromatin formation at an ectopic site, and that its repressive capacity is mediated by components of the RNA interference (RNAi) machinery. Moreover, cenH and the RNAi machinery cooperate to nucleate heterochromatin assembly at the endogenous mat locus but are dispensable for its subsequent inheritance. This work defines sequential requirements for the initiation and propagation of regional heterochromatic domains.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hall, Ira M -- Shankaranarayana, Gurumurthy D -- Noma, Ken-Ichi -- Ayoub, Nabieh -- Cohen, Amikam -- Grewal, Shiv I S -- GM59772/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2002 Sep 27;297(5590):2232-7. Epub 2002 Sep 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cold Spring Harbor Laboratory, Post Office Box 100, Cold Spring Harbor, NY 11724, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12215653" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Cell Cycle Proteins/genetics/metabolism ; Centromere ; Chromosomal Proteins, Non-Histone/metabolism ; Crosses, Genetic ; DNA, Fungal/*genetics ; Endoribonucleases/genetics/metabolism ; Enzyme Inhibitors/pharmacology ; *Gene Silencing ; Heterochromatin/*metabolism ; Histone Deacetylase Inhibitors ; Histone Deacetylases/metabolism ; Histones/metabolism ; Hydroxamic Acids/pharmacology ; Methylation ; *Methyltransferases ; Models, Genetic ; Mutation ; RNA Replicase/genetics/metabolism ; RNA, Double-Stranded/genetics/metabolism ; RNA, Fungal/*genetics/metabolism ; RNA, Small Nuclear/genetics/metabolism ; *Repetitive Sequences, Nucleic Acid ; Ribonuclease III ; Schizosaccharomyces/*genetics/metabolism ; Schizosaccharomyces pombe Proteins/genetics/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    HP1-beta mobilization promotes chromatin changes that initiate the DNA damage response (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-04-29
    Description: Minutes after DNA damage, the variant histone H2AX is phosphorylated by protein kinases of the phosphoinositide kinase family, including ATM, ATR or DNA-PK. Phosphorylated (gamma)-H2AX-which recruits molecules that sense or signal the presence of DNA breaks, activating the response that leads to repair-is the earliest known marker of chromosomal DNA breakage. Here we identify a dynamic change in chromatin that promotes H2AX phosphorylation in mammalian cells. DNA breaks swiftly mobilize heterochromatin protein 1 (HP1)-beta (also called CBX1), a chromatin factor bound to histone H3 methylated on lysine 9 (H3K9me). Local changes in histone-tail modifications are not apparent. Instead, phosphorylation of HP1-beta on amino acid Thr 51 accompanies mobilization, releasing HP1-beta from chromatin by disrupting hydrogen bonds that fold its chromodomain around H3K9me. Inhibition of casein kinase 2 (CK2), an enzyme implicated in DNA damage sensing and repair, suppresses Thr 51 phosphorylation and HP1-beta mobilization in living cells. CK2 inhibition, or a constitutively chromatin-bound HP1-beta mutant, diminishes H2AX phosphorylation. Our findings reveal an unrecognized signalling cascade that helps to initiate the DNA damage response, altering chromatin by modifying a histone-code mediator protein, HP1, but not the code itself.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ayoub, Nabieh -- Jeyasekharan, Anand D -- Bernal, Juan A -- Venkitaraman, Ashok R -- G0600332/Medical Research Council/United Kingdom -- G0700651/Medical Research Council/United Kingdom -- G9900064/Medical Research Council/United Kingdom -- MC_U105359877/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- England -- Nature. 2008 May 29;453(7195):682-6. doi: 10.1038/nature06875. Epub 2008 Apr 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Medical Research Council Cancer Cell Unit, Hutchison/MRC Research Centre, Hills Road, Cambridge CB2 0XZ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18438399" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Casein Kinase II/antagonists & inhibitors/metabolism ; Chromatin/genetics/*metabolism ; Chromosomal Proteins, Non-Histone/genetics/*metabolism ; *DNA Damage ; Fibroblasts ; Histones/metabolism ; Humans ; Hydrogen Bonding ; Methylation ; Mice ; Mutation ; Phosphorylation ; Protein Binding ; Protein Transport ; Signal Transduction
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 4
    Electronic Resource
    Electronic Resource
    The effect of particle interactions on Curie–Weiss behavior in ferrofluids (1988)
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 64 (1988), S. 5852-5854 
    Details
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The initial susceptibility of a number of Fe3 O4 particle ferrofluids with volume concentrations, ε=0.08, 0.07, 0.05, 0.03, 0.02, and 0.01 (prepared by diluting a stock fluid of Ms =40 kA m−1) has been measured in the temperature range 220–450 K. The mean particle sizes Dm (magnetic) and Dp (physical) are 74 and 81 A(ring), respectively. The ferrofluids exhibit Curie–Weiss-type behavior with negative (Néel) temperature temperature intercepts To . The form of the Curie–Weiss behavior is interpreted as arising from particle interactions which are strong enough to reduce the initial susceptibility below the noninteracting value in the temperature range of measurements. It is suggested that interactions lead to the formation of closed particle structures of zero moment in zero field and, as would be the case for an antiferromagnetic material, leads to Curie–Weiss behavior with a negative "Néel'' temperature. Negative values of To are thus characteristic of an interacting particle system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.342203
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  • 5
    Electronic Resource
    Electronic Resource
    Initial susceptibility of a textured fine particle system (1987)
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 61 (1987), S. 3305-3307 
    Details
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The initial susceptibility of a ferrofluid containing Fe3O4 particles with a lognormal distribution of volume fraction, median diameter Dvm=72 A(ring), and σ=0.4 has been measured in the temperature range 80–300 K. The measurements were taken after the sample had been cooled from the liquid to the solid state in different magnetic fields (0–5000 Oe). The effect of these fields was to introduce a "texture'' in the solid state. The initial susceptibility of the textured system was found to reach a maximum at a characteristic temperature. The value depends on the freezing field and is lower the larger the freezing field. This behavior, associated with the degree of texture, is more noticeable in samples containing a large variation in particle size, σ=0.4.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.338939
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  • 6
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    PARP1-dependent recruitment of KDM4D histone demethylase to DNA damage sites promotes double-strand break repair (2014)
    National Academy of Sciences
    Details
    Publication Date: 2014-02-03
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 7
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    DNA damage regulates the mobility of Brca2 within the nucleoplasm of living cells (2010)
    National Academy of Sciences
    Details
    Publication Date: 2010-11-22
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 8
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    Spider Transcriptomes Identify Ancient Large-Scale Gene Duplication Event Potentially Important in Silk Gland Evolution (2015)
    Oxford University Press
    Details
    Publication Date: 2015-07-05
    Description: The evolution of specialized tissues with novel functions, such as the silk synthesizing glands in spiders, is likely an influential driver of adaptive success. Large-scale gene duplication events and subsequent paralog divergence are thought to be required for generating evolutionary novelty. Such an event has been proposed for spiders, but not tested. We de novo assembled transcriptomes from three cobweb weaving spider species. Based on phylogenetic analyses of gene families with representatives from each of the three species, we found numerous duplication events indicative of a whole genome or segmental duplication. We estimated the age of the gene duplications relative to several speciation events within spiders and arachnids and found that the duplications likely occurred after the divergence of scorpions (order Scorpionida) and spiders (order Araneae), but before the divergence of the spider suborders Mygalomorphae and Araneomorphae, near the evolutionary origin of spider silk glands. Transcripts that are expressed exclusively or primarily within black widow silk glands are more likely to have a paralog descended from the ancient duplication event and have elevated amino acid replacement rates compared with other transcripts. Thus, an ancient large-scale gene duplication event within the spider lineage was likely an important source of molecular novelty during the evolution of silk gland-specific expression. This duplication event may have provided genetic material for subsequent silk gland diversification in the true spiders (Araneomorphae).
    Electronic ISSN: 1759-6653
    Topics: Biology
    Published by Oxford University Press
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  • 9
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    Ancient Properties of Spider Silks Revealed by the Complete Gene Sequence of the Prey-Wrapping Silk Protein (AcSp1) (2013)
    Oxford University Press
    Details
    Publication Date: 2013-02-06
    Description: Spider silk fibers have impressive mechanical properties and are primarily composed of highly repetitive structural proteins (termed spidroins) encoded by a single gene family. Most characterized spidroin genes are incompletely known because of their extreme size (typically 〉9 kb) and repetitiveness, limiting understanding of the evolutionary processes that gave rise to their unusual gene architectures. The only complete spidroin genes characterized thus far form the dragline in the Western black widow, Latrodectus hesperus . Here, we describe the first complete gene sequence encoding the aciniform spidroin AcSp1, the primary component of spider prey-wrapping fibers. L. hesperus AcSp1 contains a single enormous (~19 kb) exon. The AcSp1 repeat sequence is exceptionally conserved between two widow species (~94% identity) and between widows and distantly related orb-weavers (~30% identity), consistent with a history of strong purifying selection on its amino acid sequence. Furthermore, the 16 repeats (each 371–375 amino acids long) found in black widow AcSp1 are, on average, 〉99% identical at the nucleotide level. A combination of stabilizing selection on amino acid sequence, selection on silent sites, and intragenic recombination likely explains the extreme homogenization of AcSp1 repeats. In addition, phylogenetic analyses of spidroin paralogs support a gene duplication event occurring concomitantly with specialization of the aciniform glands and the tubuliform glands, which synthesize egg-case silk. With repeats that are dramatically different in length and amino acid composition from dragline spidroins, our L. hesperus AcSp1 expands the knowledge base for developing silk-based biomimetic technologies.
    Print ISSN: 0737-4038
    Electronic ISSN: 1537-1719
    Topics: Biology
    Published by Oxford University Press
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  • 10
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    Effects of Gene Duplication, Positive Selection, and Shifts in Gene Expression on the Evolution of the Venom Gland Transcriptome in Widow Spiders (2016)
    Oxford University Press
    Details
    Publication Date: 2016-01-24
    Description: Gene duplication and positive selection can be important determinants of the evolution of venom, a protein-rich secretion used in prey capture and defense. In a typical model of venom evolution, gene duplicates switch to venom gland expression and change function under the action of positive selection, which together with further duplication produces large gene families encoding diverse toxins. Although these processes have been demonstrated for individual toxin families, high-throughput multitissue sequencing of closely related venomous species can provide insights into evolutionary dynamics at the scale of the entire venom gland transcriptome. By assembling and analyzing multitissue transcriptomes from the Western black widow spider and two closely related species with distinct venom toxicity phenotypes, we do not find that gene duplication and duplicate retention is greater in gene families with venom gland biased expression in comparison with broadly expressed families. Positive selection has acted on some venom toxin families, but does not appear to be in excess for families with venom gland biased expression. Moreover, we find 309 distinct gene families that have single transcripts with venom gland biased expression, suggesting that the switching of genes to venom gland expression in numerous unrelated gene families has been a dominant mode of evolution. We also find ample variation in protein sequences of venom gland–specific transcripts, lineage-specific family sizes, and ortholog expression among species. This variation might contribute to the variable venom toxicity of these species.
    Electronic ISSN: 1759-6653
    Topics: Biology
    Published by Oxford University Press
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