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https://www.readbyqxmd.com/read/29786685/regulation-of-chromatin-states-and-gene-expression-during-hsn-neuronal-maturation-is-mediated-by-eor-1-plzf-mau-2-cohesin-loader-and-swi-snf-complex
#1
Yoichi Shinkai, Masahiro Kuramochi, Motomichi Doi
Newborn neurons mature by distinct and sequential steps through the timely induction of specific gene expression programs in concert with epigenetic changes. However, it has been difficult to investigate the relationship between gene expression and epigenetic changes at a single-cell resolution during neuronal maturation. In this study, we investigated the maturation of hermaphrodite-specific neurons (HSNs) in C. elegans, which provided the link between chromatin dynamics, gene expression, and the degree of neuronal maturation at a single-cell resolution...
May 21, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29768402/condensin-i-protects-meiotic-cohesin-from-wapl-1-mediated-removal
#2
Margarita R Hernandez, Michael B Davis, Jianhao Jiang, Elizabeth A Brouhard, Aaron F Severson, Györgyi Csankovszki
Condensin complexes are key determinants of higher-order chromatin structure and are required for mitotic and meiotic chromosome compaction and segregation. We identified a new role for condensin in the maintenance of sister chromatid cohesion during C. elegans meiosis. Using conventional and stimulated emission depletion (STED) microscopy we show that levels of chromosomally-bound cohesin were significantly reduced in dpy-28 mutants, which lack a subunit of condensin I. SYP-1, a component of the synaptonemal complex central region, was also diminished, but no decrease in the axial element protein HTP-3 was observed...
May 16, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29757144/computational-prediction-of-ctcf-cohesin-based-intra-tad-loops-that-insulate-chromatin-contacts-and-gene-expression-in-mouse-liver
#3
Bryan J Matthews, David J Waxman
CTCF and cohesin are key drivers of 3D-nuclear organization, anchoring the megabase-scale Topologically Associating Domains (TADs) that segment the genome. Here, we present and validate a computational method to predict cohesin-and-CTCF binding sites that form intra-TAD DNA loops. The intra-TAD loop anchors identified are structurally indistinguishable from TAD anchors regarding binding partners, sequence conservation, and resistance to cohesin knockdown; further, the intra-TAD loops retain key functional features of TADs, including chromatin contact insulation, blockage of repressive histone mark spread, and ubiquity across tissues...
May 14, 2018: ELife
https://www.readbyqxmd.com/read/29754905/the-post-anaphase-sumo-pathway-ensures-the-maintenance-of-centromeric-cohesion-through-meiosis-i-ii-transition-in-mammalian-oocytes
#4
Yi Ding, Masako Kaido, Elena Llano, Alberto M Pendas, Tomoya S Kitajima
The production of haploid gametes requires the maintenance of centromeric cohesion between sister chromatids through the transition between two successive meiotic divisions, meiosis I and meiosis II. One mechanism for the cohesion maintenance is shugoshin-dependent protection of centromeric cohesin at anaphase I onset [1-3]. However, how centromeric cohesion is maintained during late anaphase I and telophase I, when centromeric shugoshin is undetectable [1-3], remains largely unexplored. Here we show that the centromeric small ubiquitin-related modifier (SUMO) pathway is critical for the maintenance of centromeric cohesion during post-anaphase-I periods in mouse oocytes...
May 3, 2018: Current Biology: CB
https://www.readbyqxmd.com/read/29754816/the-cohesin-ring-uses-its-hinge-to-organize-dna-using-non-topological-as-well-as-topological-mechanisms
#5
Madhusudhan Srinivasan, Johanna C Scheinost, Naomi J Petela, Thomas G Gligoris, Maria Wissler, Sugako Ogushi, James E Collier, Menelaos Voulgaris, Alexander Kurze, Kok-Lung Chan, Bin Hu, Vincenzo Costanzo, Kim A Nasmyth
As predicted by the notion that sister chromatid cohesion is mediated by entrapment of sister DNAs inside cohesin rings, there is perfect correlation between co-entrapment of circular minichromosomes and sister chromatid cohesion. In most cells where cohesin loads without conferring cohesion, it does so by entrapment of individual DNAs. However, cohesin with a hinge domain whose positively charged lumen is neutralized loads and moves along chromatin despite failing to entrap DNAs. Thus, cohesin engages chromatin in non-topological, as well as topological, manners...
April 30, 2018: Cell
https://www.readbyqxmd.com/read/29743891/a-loss-of-function-screen-of-epigenetic-modifiers-and-splicing-factors-during-early-stage-of-cardiac-reprogramming
#6
Yang Zhou, Sahar Alimohamadi, Li Wang, Ziqing Liu, Joseph B Wall, Chaoying Yin, Jiandong Liu, Li Qian
Direct reprogramming of cardiac fibroblasts (CFs) to induced cardiomyocytes (iCMs) is a newly emerged promising approach for cardiac regeneration, disease modeling, and drug discovery. However, its potential has been drastically limited due to the low reprogramming efficiency and largely unknown underlying molecular mechanisms. We have previously screened and identified epigenetic factors related to histone modification during iCM reprogramming. Here, we used shRNAs targeting an additional battery of epigenetic factors involved in chromatin remodeling and RNA splicing factors to further identify inhibitors and facilitators of direct cardiac reprogramming...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29742289/the-genetic-and-molecular-pathogenesis-of-myelodysplastic-syndromes
#7
REVIEW
Rory M Shallis, Rami Ahmad, Amer M Zeidan
Myelodysplastic syndromes (MDS) comprise a diverse group of clonal and malignant myeloid disorders characterized by ineffective hematopoiesis, resultant peripheral cytopenias, and a meaningful increased risk of progression to acute myeloid leukemia. A wide array of recurring genetic mutations involved in RNA splicing, histone manipulation, DNA methylation, transcription factors, kinase signaling, DNA repair, cohesin proteins, and other signal transduction elements have been identified as important substrates for the development of MDS...
May 9, 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29735656/suppressor-mutation-analysis-combined-with-3d-modeling-explains-cohesin-s-capacity-to-hold-and-release-dna
#8
Xingya Xu, Ryuta Kanai, Norihiko Nakazawa, Li Wang, Chikashi Toyoshima, Mitsuhiro Yanagida
Cohesin is a fundamental protein complex that holds sister chromatids together. Separase protease cleaves a cohesin subunit Rad21/SCC1, causing the release of cohesin from DNA to allow chromosome segregation. To understand the functional organization of cohesin, we employed next-generation whole-genome sequencing and identified numerous extragenic suppressors that overcome either inactive separase/Cut1 or defective cohesin in the fission yeast Schizosaccharomyces pombe Unexpectedly, Cut1 is dispensable if suppressor mutations cause disorders of interfaces among essential cohesin subunits Psm1/SMC1, Psm3/SMC3, Rad21/SCC1, and Mis4/SCC2, the crystal structures of which suggest physical and functional impairment at the interfaces of Psm1/3 hinge, Psm1 head-Rad21, or Psm3 coiled coil-Rad21...
May 7, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29728444/emerging-evidence-of-chromosome-folding-by-loop-extrusion
#9
Geoffrey Fudenberg, Nezar Abdennur, Maxim Imakaev, Anton Goloborodko, Leonid A Mirny
Chromosome organization poses a remarkable physical problem with many biological consequences: How can molecular interactions between proteins at the nanometer scale organize micron-long chromatinized DNA molecules, insulating or facilitating interactions between specific genomic elements? The mechanism of active loop extrusion holds great promise for explaining interphase and mitotic chromosome folding, yet remains difficult to assay directly. We discuss predictions from our polymer models of loop extrusion with barrier elements and review recent experimental studies that provide strong support for loop extrusion, focusing on perturbations to CTCF and cohesin assayed via Hi-C in interphase...
May 4, 2018: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/29725056/higher-order-scaffoldin-assembly-in-ruminococcus-flavefaciens-cellulosome-is-coordinated-by-a-discrete-cohesin-dockerin-interaction
#10
Pedro Bule, Virgínia M R Pires, Victor D Alves, Ana Luísa Carvalho, José A M Prates, Luís M A Ferreira, Steven P Smith, Harry J Gilbert, Ilit Noach, Edward A Bayer, Shabir Najmudin, Carlos M G A Fontes
Cellulosomes are highly sophisticated molecular nanomachines that participate in the deconstruction of complex polysaccharides, notably cellulose and hemicellulose. Cellulosomal assembly is orchestrated by the interaction of enzyme-borne dockerin (Doc) modules to tandem cohesin (Coh) modules of a non-catalytic primary scaffoldin. In some cases, as exemplified by the cellulosome of the major cellulolytic ruminal bacterium Ruminococcus flavefaciens, primary scaffoldins bind to adaptor scaffoldins that further interact with the cell surface via anchoring scaffoldins, thereby increasing cellulosome complexity...
May 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29724914/studying-meiotic-cohesin-in-somatic-cells-reveals-that-rec8-cohesin-requires-stag3-and-is-regulated-by-wapl-and-sororin
#11
Peter G Wolf, Alexander Cuba Ramos, Julia Kenzel, Brigitte Neumann, Olaf Stemmann
The DNA embracing, ring-shaped, multiprotein complex cohesin mediates sister chromatid cohesion and is stepwise displaced in mitosis by Wapl and Separase to facilitate anaphase. Proper regulation of chromosome cohesion throughout meiosis is critical to prevent formation of aneuploid gametes, which are associated with trisomies and infertility in humans. Studying cohesion in meiocytes is complicated by their difficult experimental amenability and the absence of cohesin turnover. Here, we use cultured somatic cells to unravel fundamental aspects of meiotic cohesin...
May 3, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29724911/arf6-protects-sister-chromatid-cohesion-to-ensure-the-formation-of-stable-kinetochore-microtubule-attachments
#12
Mohamed Bourmoum, Ricardo Charles, Audrey Claing
Sister chromatid cohesion, ensured by the protein complex, cohesin, is crucial for the establishment of stable bipolar attachments of chromosomes to the spindle microtubules and their faithful segregation. Here, we demonstrate that the GTPase ARF6 prevents the premature loss of sister chromatid cohesion. During mitosis, ARF6 depleted cells normally completed chromosome congression. However, at the metaphase plate, chromosomes failed to establish stable kinetochore-microtubule attachments because of the impaired cohesion at centromeres...
May 3, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29706548/the-energetics-and-physiological-impact-of-cohesin-extrusion
#13
Laura Vian, Aleksandra Pękowska, Suhas S P Rao, Kyong-Rim Kieffer-Kwon, Seolkyoung Jung, Laura Baranello, Su-Chen Huang, Laila El Khattabi, Marei Dose, Nathanael Pruett, Adrian L Sanborn, Andres Canela, Yaakov Maman, Anna Oksanen, Wolfgang Resch, Xingwang Li, Byoungkoo Lee, Alexander L Kovalchuk, Zhonghui Tang, Steevenson Nelson, Michele Di Pierro, Ryan R Cheng, Ido Machol, Brian Glenn St Hilaire, Neva C Durand, Muhammad S Shamim, Elena K Stamenova, José N Onuchic, Yijun Ruan, Andre Nussenzweig, David Levens, Erez Lieberman Aiden, Rafael Casellas
Cohesin extrusion is thought to play a central role in establishing the architecture of mammalian genomes. However, extrusion has not been visualized in vivo, and thus, its functional impact and energetics are unknown. Using ultra-deep Hi-C, we show that loop domains form by a process that requires cohesin ATPases. Once formed, however, loops and compartments are maintained for hours without energy input. Strikingly, without ATP, we observe the emergence of hundreds of CTCF-independent loops that link regulatory DNA...
April 24, 2018: Cell
https://www.readbyqxmd.com/read/29702522/three-dimensional-genome-organization-in-normal-and-malignant-haematopoiesis
#14
Sergi Cuartero, Matthias Merkenschlager
PURPOSE OF REVIEW: The three-dimensional organization of the genome inside the nucleus impacts on key aspects of genome function, including transcription, DNA replication and repair. The chromosome maintenance complex cohesin and the DNA binding protein CTCF cooperate to drive the formation of self-interacting topological domains. This facilitates transcriptional regulation via enhancer-promoter interactions, controls the distribution and release of torsional strain, and affects the frequency with which particular translocations arise, based on the spatial proximity of translocation partners...
April 26, 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29697484/cohesin-in-haematopoiesis-and-leukaemia
#15
Roman Galeev, Jonas Larsson
PURPOSE OF REVIEW: Disturbance of the delicate balance between self-renewal and differentiation in haematopoietic stem cells (HSCs) can lead to both leukaemia and bone marrow failure. The regulation of this balance in HSC biology has been intensely investigated in several model systems, and lately the importance of epigenetic modifications as well as the organization and architecture of chromatin has become increasingly recognized. In this review, we will focus on the role of the chromatin organizing protein complex cohesin in regulation of normal and malignant haematopoiesis...
April 24, 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29695489/dynamics-of-sister-chromatid-resolution-during-cell-cycle-progression
#16
Rugile Stanyte, Johannes Nuebler, Claudia Blaukopf, Rudolf Hoefler, Roman Stocsits, Jan-Michael Peters, Daniel W Gerlich
Faithful genome transmission in dividing cells requires that the two copies of each chromosome's DNA package into separate but physically linked sister chromatids. The linkage between sister chromatids is mediated by cohesin, yet where sister chromatids are linked and how they resolve during cell cycle progression has remained unclear. In this study, we investigated sister chromatid organization in live human cells using dCas9-mEGFP labeling of endogenous genomic loci. We detected substantial sister locus separation during G2 phase irrespective of the proximity to cohesin enrichment sites...
April 25, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29692343/clonal-interference-of-signaling-mutations-holds-prognostic-relevance-in-core-binding-factor-acute-myeloid-leukemia
#17
Raphael Itzykson, Nicolas Duployez, Annette Fasan, Gauthier Decool, Alice Marceau-Renaut, Manja Meggendorfer, Eric Jourdan, Arnaud Petit, Hélène Lapillonne, Jean-Baptiste Micol, Pascale Cornillet-Lefebvre, Norbert Ifrah, Guy Leverger, Hervé Dombret, Nicolas Boissel, Torsten Haferlach, Claude Preudhomme
Mutations in receptor tyrosine kinase/RAS signaling pathway genes are frequent in Core Binding Factor Acute Myeloid Leukemias (CBF AML), but their prognostic relevance is debated. A subset of CBF AML patients harbors several signaling gene mutations. Genotyping of colonies and of relapse samples indicates that these arise in independent clones, thus defining a process of clonal interference (or parallel evolution). Clonal interference is pervasive in cancers but the mechanisms underlying this process remain unclear, and its prognostic impact unknown...
April 24, 2018: Blood
https://www.readbyqxmd.com/read/29685368/principles-of-chromosome-architecture-revealed-by-hi-c
#18
REVIEW
Kyle P Eagen
Chromosomes are folded and compacted in interphase nuclei, but the molecular basis of this folding is poorly understood. Chromosome conformation capture methods, such as Hi-C, combine chemical crosslinking of chromatin with fragmentation, DNA ligation, and high-throughput DNA sequencing to detect neighboring loci genome-wide. Hi-C has revealed the segregation of chromatin into active and inactive compartments and the folding of DNA into self-associating domains and loops. Depletion of CTCF, cohesin, or cohesin-associated proteins was recently shown to affect the majority of domains and loops in a manner that is consistent with a model of DNA folding through extrusion of chromatin loops...
April 20, 2018: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/29667147/effects-of-heyan-kuntai-capsule-on-follicular-development-and-oocyte-cohesin-levels-in-aged-mice
#19
Bin Zhang, Nan Chu, Xue-Min Qiu, Wei Tang, Hans-Jürgen Gober, Da-Jin Li, Ling Wang
OBJECTIVE: To evaluate the effect of Heyan Kuntai Capsule (, HYKT) on the ovarian function of aged mice and expressions of cohesion complexes in oocytes. METHODS: Twenty-five 9-month-old female C57BL/6J mice were randomly divided into 5 groups by block randomization method (n=5 per group), including the control group (saline), 17 β-estradiol group [E2 , 100 μg/(kg·d)], and low-, medium-, and high-dose of HYKT groups [0.3, 0.9, 2.7 g/(kg·d), respectively]. All mice were treated by intragastric administration for 4 weeks...
April 17, 2018: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/29662124/stag2-deficiency-induces-interferon-responses-via-cgas-sting-pathway-and-restricts-virus-infection
#20
Siyuan Ding, Jonathan Diep, Ningguo Feng, Lili Ren, Bin Li, Yaw Shin Ooi, Xin Wang, Kevin F Brulois, Linda L Yasukawa, Xingnan Li, Calvin J Kuo, David A Solomon, Jan E Carette, Harry B Greenberg
Cohesin is a multi-subunit nuclear protein complex that coordinates sister chromatid separation during cell division. Highly frequent somatic mutations in genes encoding core cohesin subunits have been reported in multiple cancer types. Here, using a genome-wide CRISPR-Cas9 screening approach to identify host dependency factors and novel innate immune regulators of rotavirus (RV) infection, we demonstrate that the loss of STAG2, an important component of the cohesin complex, confers resistance to RV replication in cell culture and human intestinal enteroids...
April 16, 2018: Nature Communications
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