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https://www.readbyqxmd.com/read/28087629/jmjd2c-kdm4c-facilitates-the-assembly-of-essential-enhancer-protein-complexes-at-the-onset-of-embryonic-stem-cell-differentiation
#1
Rute A Tomaz, Jennifer L Harman, Donja Karimlou, Lauren Weavers, Lauriane Fritsch, Tony Bou-Kheir, Emma Bell, Ignacio Del Valle Torres, Kathy K Niakan, Cynthia Fisher, Onkar Joshi, Hendrik G Stunnenberg, Edward Curry, Slimane Ait-Si-Ali, Helle F Jørgensen, Véronique Azuara
Jmjd2/Kdm4 H3K9-demethylases cooperate in promoting mouse embryonic stem cell (ESC) identity. However, little is known about their importance at the exit of ESC pluripotency. Here, we uncover that Jmjd2c facilitates this process by stabilizing the assembly of Mediator-Cohesin complexes at lineage-specific enhancers. Functionally, we show that Jmjd2c is required in ESCs to initiate appropriate gene expression programs upon somatic multi-lineage differentiation. In the absence of Jmjd2c, differentiation is stalled at an early post-implantation epiblast-like stage, while Jmjd2c-knockout ESCs remain capable of forming extra-embryonic endoderm derivatives...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28063196/asxl2-mutations-are-frequently-found-in-pediatric-aml-patients-with-t-8-21-runx1-runx1t1-and-associated-with-a-better-prognosis
#2
Genki Yamato, Norio Shiba, Kenichi Yoshida, Yuichi Shiraishi, Yusuke Hara, Kentaro Ohki, Jun Okubo, Haruna Okuno, Kenichi Chiba, Hiroko Tanaka, Akitoshi Kinoshita, Hiroshi Moritake, Nobutaka Kiyokawa, Daisuke Tomizawa, Myoung-Ja Park, Manabu Sotomatsu, Takashi Taga, Souichi Adachi, Akio Tawa, Keizo Horibe, Hirokazu Arakawa, Satoru Miyano, Seishi Ogawa, Yasuhide Hayashi
ASXL2 is an epigenetic regulator involved in polycomb repressive complex regulation or recruitment. Clinical features of pediatric AML patients with ASXL2 mutations remain unclear. Thus, we investigated frequencies of ASXL1 and ASXL2 mutations, clinical features of patients with these mutations, correlations of these mutations with other genetic alterations including BCOR/BCORL1 and cohesin complex component genes, and prognostic impact of these mutations in 369 pediatric patients with de novo AML (0-17 years)...
January 7, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28062851/human-cactin-interacts-with-dhx8-and-srrm2-to-assure-efficient-pre-mrna-splicing-and-sister-chromatid-cohesion
#3
Isabella M Y Zanini, Charlotte Soneson, Luca E Lorenzi, Claus M Azzalin
Cactins constitute a family of eukaryotic proteins broadly conserved from yeast to human and required for fundamental processes such as cell proliferation, genome stability maintenance, organismal development and immune response. Cactin proteins have been found to associate with the spliceosome in several model organisms, nevertheless their molecular functions await elucidation. Here we show that depletion of human Cactin (hCactin) leads to premature sister chromatid separation, genome instability and cell proliferation arrest...
January 6, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28059076/structure-of-the-cohesin-loader-scc2
#4
William C H Chao, Yasuto Murayama, Sofía Muñoz, Andrew W Jones, Benjamin O Wade, Andrew G Purkiss, Xiao-Wen Hu, Aaron Borg, Ambrosius P Snijders, Frank Uhlmann, Martin R Singleton
The functions of cohesin are central to genome integrity, chromosome organization and transcription regulation through its prevention of premature sister-chromatid separation and the formation of DNA loops. The loading of cohesin onto chromatin depends on the Scc2-Scc4 complex; however, little is known about how it stimulates the cohesion-loading activity. Here we determine the large 'hook' structure of Scc2 responsible for catalysing cohesin loading. We identify key Scc2 surfaces that are crucial for cohesin loading in vivo...
January 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28057211/roles-of-smc-complexes-during-t-lymphocyte-development-and-function
#5
J S Rawlings
T lymphocytes (T cells) comprise a critical component of the immune system charged with diverse functions during an immune response. As a function of maturation in the thymus, T cells become quiescent and remain so until they participate in an immune response in the periphery. Recent work indicates that the control of T cell proliferation is mediated, at least in part, by chromatin architecture. Quiescent T cells possess a condensed chromatin, whereas proliferating T cells have a more open chromatin configuration...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28050734/sororin-is-enriched-at-the-central-region-of-synapsed-meiotic-chromosomes
#6
Philip W Jordan, Craig Eyster, Jingrong Chen, Roberto J Pezza, Susannah Rankin
During meiotic prophase, cohesin complexes mediate cohesion between sister chromatids and promote pairing and synapsis of homologous chromosomes. Precisely how the activity of cohesin is controlled to promote these events is not fully understood. In metazoans, cohesion establishment between sister chromatids during mitotic divisions is accompanied by recruitment of the cohesion-stabilizing protein Sororin. During somatic cell division cycles, Sororin is recruited in response to DNA replication-dependent modification of the cohesin complex by ESCO acetyltransferases...
January 3, 2017: Chromosome Research
https://www.readbyqxmd.com/read/28041881/nipbl-interacts-with-zfp609-and-the-integrator-complex-to-regulate-cortical-neuron-migration
#7
Debbie L C van den Berg, Roberta Azzarelli, Koji Oishi, Ben Martynoga, Noelia Urbán, Dick H W Dekkers, Jeroen A Demmers, François Guillemot
Mutations in NIPBL are the most frequent cause of Cornelia de Lange syndrome (CdLS), a developmental disorder encompassing several neurological defects, including intellectual disability and seizures. How NIPBL mutations affect brain development is not understood. Here we identify Nipbl as a functional interaction partner of the neural transcription factor Zfp609 in brain development. Depletion of Zfp609 or Nipbl from cortical neural progenitors in vivo is detrimental to neuronal migration. Zfp609 and Nipbl overlap at genomic binding sites independently of cohesin and regulate genes that control cortical neuron migration...
December 20, 2016: Neuron
https://www.readbyqxmd.com/read/28017619/casein-kinase-1-coordinates-cohesin-cleavage-gametogenesis-and-exit-from-m-phase-in-meiosis-ii
#8
Orlando Argüello-Miranda, Ievgeniia Zagoriy, Valentina Mengoli, Julie Rojas, Katarzyna Jonak, Tugce Oz, Peter Graf, Wolfgang Zachariae
Meiosis consists of DNA replication followed by two consecutive nuclear divisions and gametogenesis or spore formation. While meiosis I has been studied extensively, less is known about the regulation of meiosis II. Here we show that Hrr25, the conserved casein kinase 1δ of budding yeast, links three mutually independent key processes of meiosis II. First, Hrr25 induces nuclear division by priming centromeric cohesin for cleavage by separase. Hrr25 simultaneously phosphorylates Rec8, the cleavable subunit of cohesin, and removes from centromeres the cohesin protector composed of shugoshin and the phosphatase PP2A...
January 9, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28005992/do-exogenous-dna-double-strand-breaks-change-incomplete-synapsis-and-chiasma-localization-in-the-grasshopper-stethophyma-grossum
#9
Adela Calvente, Juan Luis Santos, Julio S Rufas
Meiotic recombination occurs as a programmed event that initiates by the formation of DNA double-strand breaks (DSBs) that give rise to the formation of crossovers that are observed as chiasmata. Chiasmata are essential for the accurate chromosome segregation and the generation of new combinations of parental alleles. Some treatments that provoke exogenous DSBs also lead to alterations in the recombination pattern of some species in which full homologous synapsis is achieved at pachytene. We have carried out a similar approach in males of the grasshopper Stethophyma grossum, whose homologues show incomplete synapsis and proximal chiasma localization...
2016: PloS One
https://www.readbyqxmd.com/read/27996020/naa50-san-dependent-n-terminal-acetylation-of-scc1-is-potentially-important-for-sister-chromatid-cohesion
#10
Ana Luisa Ribeiro, Rui D Silva, Håvard Foyn, Margarida N Tiago, Om Singh Rathore, Thomas Arnesen, Rui Gonçalo Martinho
The gene separation anxiety (san) encodes Naa50/San, a N-terminal acetyltransferase required for chromosome segregation during mitosis. Although highly conserved among higher eukaryotes, the mitotic function of this enzyme is still poorly understood. Naa50/San was originally proposed to be required for centromeric sister chromatid cohesion in Drosophila and human cells, yet, more recently, it was also suggested to be a negative regulator of microtubule polymerization through internal acetylation of beta Tubulin...
December 20, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27991799/mechanical-stability-of-a-high-affinity-toxin-anchor-from-the-pathogen-clostridium-perfringens
#11
Lukas F Milles, Edward A Bayer, Michael A Nash, Hermann E Gaub
The opportunistic pathogen Clostridium perfringens assembles its toxins and carbohydrate-active enzymes by the high-affinity cohesin-dockerin (Coh-Doc) interaction. Coh-Doc interactions characterized previously have shown considerable resilience toward mechanical stress. Here, we aimed to determine the mechanics of this interaction from C. perfringens in the context of a pathogen. Using atomic force microscopy based single-molecule force spectroscopy (AFM-SMFS) we probed the mechanical properties of the interaction of a dockerin from the μ-toxin with the GH84C X82 cohesin domain of C...
December 19, 2016: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/27984718/a-zygotic-checkpoint-for-unrepaired-lesions
#12
Lee Zou
DNA demethylation, a process involving DNA repair, is critical for reprogramming of the paternal genome during the oocyte-to-zygote transition. A new study by Ladstätter and Tachibana-Konwalski shows that a Chk1-mediated zygotic checkpoint monitors the cohesin-dependent repair of DNA lesions arising from DNA demethylation, which prevents zygotes carrying unrepaired lesions from entering mitosis.
December 15, 2016: Cell
https://www.readbyqxmd.com/read/27977916/spore-displayed-enzyme-cascade-with-tunable-stoichiometry
#13
Long Chen, Ashok Mulchandani, Xin Ge
Taking the advantages of inert and stable nature of endospores, we developed a biocatalysis platform for multiple enzyme immobilization on Bacillus subtilis spore surface. Among B. subtilis outer coat proteins, CotG mediated a high expression level of Clostridium thermocellum cohesin (CtCoh) with a functional display capability of ∼10(4) molecules per spore of xylose reductase C. termocellum dockerin fusion protein (XR-CtDoc). By co-immobilization of phosphite dehydrogenase (PTDH) on spore surface via Ruminococcus flavefaciens cohesin-dockerin modules, regeneration of NADPH was achieved...
December 15, 2016: Biotechnology Progress
https://www.readbyqxmd.com/read/27974201/functional-mutations-form-at-ctcf-cohesin-binding-sites-in-melanoma-due-to-uneven-nucleotide-excision-repair-across-the-motif
#14
Rebecca C Poulos, Julie A I Thoms, Yi Fang Guan, Ashwin Unnikrishnan, John E Pimanda, Jason W H Wong
CTCF binding sites are frequently mutated in cancer, but how these mutations accumulate and whether they broadly perturb CTCF binding are not well understood. Here, we report that skin cancers exhibit a highly specific asymmetric mutation pattern within CTCF motifs attributable to ultraviolet irradiation and differential nucleotide excision repair (NER). CTCF binding site mutations form independently of replication timing and are enriched at sites of CTCF/cohesin complex binding, suggesting a role for cohesin in stabilizing CTCF-DNA binding and impairing NER...
December 13, 2016: Cell Reports
https://www.readbyqxmd.com/read/27966791/separase-function-beyond-cohesion-cleavage-and-an-emerging-oncogene
#15
Ravinder Kumar
Proper and timely segregation of genetic endowment is necessary for survival and perpetuation of every species. Mis-segregation of chromosomes and resulting aneuploidy leads to genetic instability, which can jeopardize the survival of an individual or population as a whole. Abnormality with segregation of genetic contents has been associated with several medical consequences including cancer, sterility, mental retardation, spontaneous abortion, miscarriages and other birth related defects. Separase, by irreversible cleavage of cohesin complex subunit, paves the way for metaphase/anaphase transition during the cell cycle...
December 14, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27941816/cellulosomes-bacterial-nanomachines-for-dismantling-plant-polysaccharides
#16
Lior Artzi, Edward A Bayer, Sarah Moraïs
Cellulosomes are multienzyme complexes that are produced by anaerobic cellulolytic bacteria for the degradation of lignocellulosic biomass. They comprise a complex of scaffoldin, which is the structural subunit, and various enzymatic subunits. The intersubunit interactions in these multienzyme complexes are mediated by cohesin and dockerin modules. Cellulosome-producing bacteria have been isolated from a large variety of environments, which reflects their prevalence and the importance of this microbial enzymatic strategy...
December 12, 2016: Nature Reviews. Microbiology
https://www.readbyqxmd.com/read/27932493/prdm9-interactions-with-other-proteins-provide-a-link-between-recombination-hotspots-and-the-chromosomal-axis-in-meiosis
#17
Emil D Parvanov, Hui Tian, Timothy Billings, Ruth L Saxl, Catrina Spruce, Rakesh Aithal, Lumir Krejci, Kenneth Paigen, Petko M Petkov
In mammals, meiotic recombination occurs at 1-2 kb genomic regions termed hotspots, whose positions and activities are determined by PRDM9, a DNA-binding histone methyltransferase. We now show that the KRAB domain of PRDM9 forms complexes with additional proteins to allow hotspots to proceed into the next phase of recombination. By a combination of yeast-two hybrid assay, in vitro binding, and co-immunoprecipitation from mouse spermatocytes, we identified four proteins that directly interact with PRDM9's KRAB domain, namely CXXC1, EWSR1, EHMT2, and CDYL...
December 8, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27924829/diverse-specificity-of-cellulosome-attachment-to-the-bacterial-cell-surface
#18
Joana L A Brás, Benedita A Pinheiro, Kate Cameron, Fiona Cuskin, Aldino Viegas, Shabir Najmudin, Pedro Bule, Virginia M R Pires, Maria João Romão, Edward A Bayer, Holly L Spencer, Steven Smith, Harry J Gilbert, Victor D Alves, Ana Luísa Carvalho, Carlos M G A Fontes
During the course of evolution, the cellulosome, one of Nature's most intricate multi-enzyme complexes, has been continuously fine-tuned to efficiently deconstruct recalcitrant carbohydrates. To facilitate the uptake of released sugars, anaerobic bacteria use highly ordered protein-protein interactions to recruit these nanomachines to the cell surface. Dockerin modules located within a non-catalytic macromolecular scaffold, whose primary role is to assemble cellulosomal enzymatic subunits, bind cohesin modules of cell envelope proteins, thereby anchoring the cellulosome onto the bacterial cell...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27924011/roles-for-aprin-pds5b-in-homologous-recombination-and-in-ovarian-cancer-prediction
#19
Anthony M Couturier, Hubert Fleury, Anne-Marie Patenaude, Victoria L Bentley, Amélie Rodrigue, Yan Coulombe, Joshi Niraj, Joris Pauty, Jason N Berman, Graham Dellaire, Javier M Di Noia, Anne-Marie Mes-Masson, Jean-Yves Masson
APRIN (PDS5 cohesin associated factor B) interacts with both the cohesin complex and the BRCA2 tumor suppressor. How APRIN influences cohesion and DNA repair processes is not well understood. Here, we show that APRIN is recruited to DNA damage sites. We find that APRIN interacts directly with RAD51, PALB2 and BRCA2. APRIN stimulates RAD51-mediated DNA strand invasion. APRIN also binds DNA with an affinity for D-loop structures and single-strand (ss) DNA. APRIN is a new homologous recombination (HR) mediator as it counteracts the RPA inhibitory effect on RAD51 loading to ssDNA...
December 15, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27917322/bioinformatical-analysis-of-eukaryotic-shugoshins-reveals-meiosis-specific-features-of-vertebrate-shugoshins
#20
Tatiana M Grishaeva, Darya Kulichenko, Yuri F Bogdanov
BACKGROUND: Shugoshins (SGOs) are proteins that protect cohesins located at the centromeres of sister chromatids from their early cleavage during mitosis and meiosis in plants, fungi, and animals. Their function is to prevent premature sister-chromatid disjunction and segregation. The study focused on the structural differences among SGOs acting during mitosis and meiosis that cause differences in chromosome behavior in these two types of cell division in different organisms. METHODS: A bioinformatical analysis of protein domains, conserved amino acid motifs, and physicochemical properties of 32 proteins from 25 species of plants, fungi, and animals was performed...
2016: PeerJ
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