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https://www.readbyqxmd.com/read/28525758/targeted-degradation-of-ctcf-decouples-local-insulation-of-chromosome-domains-from-genomic-compartmentalization
#1
Elphège P Nora, Anton Goloborodko, Anne-Laure Valton, Johan H Gibcus, Alec Uebersohn, Nezar Abdennur, Job Dekker, Leonid A Mirny, Benoit G Bruneau
The molecular mechanisms underlying folding of mammalian chromosomes remain poorly understood. The transcription factor CTCF is a candidate regulator of chromosomal structure. Using the auxin-inducible degron system in mouse embryonic stem cells, we show that CTCF is absolutely and dose-dependently required for looping between CTCF target sites and insulation of topologically associating domains (TADs). Restoring CTCF reinstates proper architecture on altered chromosomes, indicating a powerful instructive function for CTCF in chromatin folding...
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28525739/genome-organization-cohesin-on-the-move
#2
Judita Richterova, Barbora Huraiova, Juraj Gregan
Folding of mammalian genomes into spatial domains is thought to depend on cohesin and CTCF proteins. Busslinger et al. (2017) reveal that transcription moves cohesin along DNA to CTCF-binding sites, providing insights into how cohesin and CTCF mediate chromosomal interactions by formation of chromatin loops.
May 18, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28513628/an-integrated-model-for-detecting-significant-chromatin-interactions-from-high-resolution-hi-c-data
#3
Mark Carty, Lee Zamparo, Merve Sahin, Alvaro González, Raphael Pelossof, Olivier Elemento, Christina S Leslie
Here we present HiC-DC, a principled method to estimate the statistical significance (P values) of chromatin interactions from Hi-C experiments. HiC-DC uses hurdle negative binomial regression account for systematic sources of variation in Hi-C read counts-for example, distance-dependent random polymer ligation and GC content and mappability bias-and model zero inflation and overdispersion. Applied to high-resolution Hi-C data in a lymphoblastoid cell line, HiC-DC detects significant interactions at the sub-topologically associating domain level, identifying potential structural and regulatory interactions supported by CTCF binding sites, DNase accessibility, and/or active histone marks...
May 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28506242/an-imprinted-non-coding-genomic-cluster-at-14q32-defines-clinically-relevant-molecular-subtypes-in-osteosarcoma-across-multiple-independent-datasets
#4
Katherine E Hill, Andrew D Kelly, Marieke L Kuijjer, William Barry, Ahmed Rattani, Cassandra C Garbutt, Haydn Kissick, Katherine Janeway, Antonio Perez-Atayde, Jeffrey Goldsmith, Mark C Gebhardt, Mohamed S Arredouani, Greg Cote, Francis Hornicek, Edwin Choy, Zhenfeng Duan, John Quackenbush, Benjamin Haibe-Kains, Dimitrios Spentzos
BACKGROUND: A microRNA (miRNA) collection on the imprinted 14q32 MEG3 region has been associated with outcome in osteosarcoma. We assessed the clinical utility of this miRNA set and their association with methylation status. METHODS: We integrated coding and non-coding RNA data from three independent annotated clinical osteosarcoma cohorts (n = 65, n = 27, and n = 25) and miRNA and methylation data from one in vitro (19 cell lines) and one clinical (NCI Therapeutically Applicable Research to Generate Effective Treatments (TARGET) osteosarcoma dataset, n = 80) dataset...
May 15, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28504305/intranuclear-and-higher-order-chromatin-organization-of-the-major-histone-gene-cluster-in-breast-cancer
#5
Andrew J Fritz, Prachi N Ghule, Joseph R Boyd, Coralee E Tye, Natalie A Page, Deli Hong, Adam S Weinheimer, A Rasim Barutcu, Diana L Gerrard, Seth Frietze, Sayyed K Zaidi, Anthony Imbalzano, Jane B Lian, Janet L Stein, Gary S Stein
Alterations in nuclear morphology are common in cancer progression. However, the degree to which gross morphological abnormalities translate into compromised higher-order chromatin organization is poorly understood. To explore the functional links between gene expression and chromatin structure in breast cancer, we performed RNA-seq gene expression analysis on the basal breast cancer progression model based on human MCF10A cells. Positional gene enrichment identified the major histone gene cluster at chromosome 6p22 as one of the most significantly upregulated (and not amplified) clusters of genes from the normal-like MCF10A to premalignant MCF10AT1 and metastatic MCF10CA1a cells...
May 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28490592/epstein-barr-virus-rta-mediated-accumulation-of-dna-methylation-interferes-with-ctcf-binding-in-both-host-and-viral-genomes
#6
Yen-Ju Chen, Yu-Lian Chen, Yao Chang, Chung-Chun Wu, Ying-Chieh Ko, Sai Wah Tsao, Jen-Yang Chen, Su-Fang Lin
Rta, an Epstein-Barr virus (EBV) immediate-early protein, reactivates viral lytic replication that is closely associated with tumorigenesis. In previous studies, we demonstrated that in epithelial cells Rta efficiently induced cellular senescence, which is an irreversible G1 arrest likely to provide a favorable environment for productive replications of EBV and Kaposi's sarcoma-associated herpesvirus (KSHV). To restrict progression of the cell cycle, Rta simultaneously upregulates CDK inhibitors and downregulates MYC, CCND1 and JUN, among others...
May 10, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28487148/direct-observation-of-cell-cycle-dependent-interactions-between-ctcf-and-chromatin
#7
Harsha Agarwal, Matthias Reisser, Celina Wortmann, J Christof M Gebhardt
The three-dimensional arrangement of chromatin encodes regulatory traits important for nuclear processes such as transcription and replication. Chromatin topology is in part mediated by the architectural protein CCCTC-binding factor (CTCF) that binds to the boundaries of topologically associating domains. Whereas sites of CTCF interactions are well characterized, little is known on how long CTCF binds to chromatin and how binding evolves during the cell cycle. We monitored CTCF-chromatin interactions by live cell single molecule tracking in different phases of the cell cycle...
May 6, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28483487/mechanical-stress-affects-methylation-pattern-of-gnas-isoforms-and-osteogenic-differentiation-of-hat-mscs
#8
Angeliki-Maria Vlaikou, Dimitrios Kouroupis, Argyro Sgourou, Georgios S Markopoulos, Eleni Bagli, Maria Markou, Zoe Papadopoulou, Theodore Fotsis, Georgios Nakos, Maria-Eleni E Lekka, Maria Syrrou
Mechanical stress exerts a substantial role on skeletal-cell renewal systems, whereas accumulating evidence suggests that epigenetic mechanisms induce changes and differential gene expression. Although the underlying mechanisms remain to be fully elucidated, our study suggests that the influence of the long term mechanical stimulation elicits epigenetic modifications controlling osteogenic differentiation of human adipose tissue multipotential stromal cells (hAT-MSCs) and contributes to an accelerating in vitro osteogenesis...
May 5, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28475897/the-cohesin-release-factor-wapl-restricts-chromatin-loop-extension
#9
Judith H I Haarhuis, Robin H van der Weide, Vincent A Blomen, J Omar Yáñez-Cuna, Mario Amendola, Marjon S van Ruiten, Peter H L Krijger, Hans Teunissen, René H Medema, Bas van Steensel, Thijn R Brummelkamp, Elzo de Wit, Benjamin D Rowland
The spatial organization of chromosomes influences many nuclear processes including gene expression. The cohesin complex shapes the 3D genome by looping together CTCF sites along chromosomes. We show here that chromatin loop size can be increased and that the duration with which cohesin embraces DNA determines the degree to which loops are enlarged. Cohesin's DNA release factor WAPL restricts this loop extension and also prevents looping between incorrectly oriented CTCF sites. We reveal that the SCC2/SCC4 complex promotes the extension of chromatin loops and the formation of topologically associated domains (TADs)...
May 4, 2017: Cell
https://www.readbyqxmd.com/read/28467369/developmental-control-of-nramp1-slc11a1-expression-in-professional-phagocytes
#10
Mathieu F M Cellier
NRAMP1 (SLC11A1) is a professional phagocyte membrane importer of divalent metals that contributes to iron recycling at homeostasis and to nutritional immunity against infection. Analyses of data generated by several consortia and additional studies were integrated to hypothesize mechanisms restricting NRAMP1 expression to mature phagocytes. Results from various epigenetic and transcriptomic approaches were collected for mesodermal and hematopoietic cell types and compiled for combined analysis with results of genetic studies associating single nucleotide polymorphisms (SNPs) with variations in NRAMP1 expression (eQTLs)...
May 3, 2017: Biology
https://www.readbyqxmd.com/read/28467304/ctcf-and-cohesin-regulate-chromatin-loop-stability-with-distinct-dynamics
#11
Anders S Hansen, Iryna Pustova, Claudia Cattoglio, Robert Tjian, Xavier Darzacq
Folding of mammalian genomes into spatial domains is critical for gene regulation. The insulator protein CTCF and cohesin control domain location by folding domains into loop structures, which are widely thought to be stable. Combining genomic and biochemical approaches we show that CTCF and cohesin co-occupy the same sites and physically interact as a biochemically stable complex. However, using single-molecule imaging we find that CTCF binds chromatin much more dynamically than cohesin (~1-2 min vs. ~22 min residence time)...
May 3, 2017: ELife
https://www.readbyqxmd.com/read/28464923/enriching-the-international-clinical-nomenclature-with-chinese-daily-used-synonyms-and-concept-recognition-in-physician-notes
#12
Rui Zhang, Jialin Liu, Yong Huang, Miye Wang, Qingke Shi, Jun Chen, Zhi Zeng
BACKGROUND: It has been shown that the entities in everyday clinical text are often expressed in a way that varies from how they are expressed in the nomenclature. Owing to lots of synonyms, abbreviations, medical jargons or even misspellings in the daily used physician notes in clinical information system (CIS), the terminology without enough synonyms may not be adequately suitable for the task of Chinese clinical term recognition. METHODS: This paper demonstrates a validated system to retrieve the Chinese term of clinical finding (CTCF) from CIS and map them to the corresponding concepts of international clinical nomenclature, such as SNOMED CT...
May 2, 2017: BMC Medical Informatics and Decision Making
https://www.readbyqxmd.com/read/28456021/parp1-restricts-epstein-barr-virus-lytic-reactivation-by-binding-the-bzlf1-promoter
#13
Lena N Lupey-Green, Stephanie A Moquin, Kayla A Martin, Shane M McDevitt, Michael Hulse, Lisa B Caruso, Richard T Pomerantz, Jj L Miranda, Italo Tempera
The Epstein Barr virus (EBV) genome persists in infected host cells as a chromatinized episome and is subject to chromatin-mediated regulation. Binding of the host insulator protein CTCF to the EBV genome has an established role in maintaining viral latency type, and in other herpesviruses, loss of CTCF binding at specific regions correlates with viral reactivation. Here, we demonstrate that binding of PARP1, an important cofactor of CTCF, at the BZLF1 lytic switch promoter restricts EBV reactivation. Knockdown of PARP1 in the Akata-EBV cell line significantly increases viral copy number and lytic protein expression...
April 26, 2017: Virology
https://www.readbyqxmd.com/read/28436944/active-and-poised-promoter-states-drive-folding-of-the-extended-hoxb-locus-in-mouse-embryonic-stem-cells
#14
Mariano Barbieri, Sheila Q Xie, Elena Torlai Triglia, Andrea M Chiariello, Simona Bianco, Inês de Santiago, Miguel R Branco, David Rueda, Mario Nicodemi, Ana Pombo
Gene expression states influence the 3D conformation of the genome through poorly understood mechanisms. Here, we investigate the conformation of the murine HoxB locus, a gene-dense genomic region containing closely spaced genes with distinct activation states in mouse embryonic stem (ES) cells. To predict possible folding scenarios, we performed computer simulations of polymer models informed with different chromatin occupancy features that define promoter activation states or binding sites for the transcription factor CTCF...
April 24, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28428255/nucleosome-nucleosome-interactions-via-histone-tails-and-linker-dna-regulate-nuclear-rigidity
#15
Yuta Shimamoto, Sachiko Tamura, Hiroshi Masumoto, Kazuhiro Maeshima
Cells, as well as the nuclei inside them, experience significant mechanical stress in diverse biological processes including contraction, migration, and adhesion. The structural stability of nuclei must therefore be maintained in order to protect genome integrity. Despite extensive knowledge on nuclear architecture and components, however, the underlying physical and molecular mechanisms remain largely unknown. We addressed this in the present study by subjecting isolated human cell nuclei to microneedle-based quantitative micromanipulation with a series of biochemical perturbations of the chromatin...
April 20, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28424523/cohesin-is-positioned-in-mammalian-genomes-by-transcription-ctcf-and-wapl
#16
Georg A Busslinger, Roman R Stocsits, Petra van der Lelij, Elin Axelsson, Antonio Tedeschi, Niels Galjart, Jan-Michael Peters
Mammalian genomes are spatially organized by CCCTC-binding factor (CTCF) and cohesin into chromatin loops and topologically associated domains, which have important roles in gene regulation and recombination. By binding to specific sequences, CTCF defines contact points for cohesin-mediated long-range chromosomal cis-interactions. Cohesin is also present at these sites, but has been proposed to be loaded onto DNA elsewhere and to extrude chromatin loops until it encounters CTCF bound to DNA. How cohesin is recruited to CTCF sites, according to this or other models, is unknown...
April 19, 2017: Nature
https://www.readbyqxmd.com/read/28424352/chromatin-module-inference-on-cellular-trajectories-identifies-key-transition-points-and-poised-epigenetic-states-in-diverse-developmental-processes
#17
Sushmita Roy, Rupa Sridharan
Changes in chromatin state play important roles in cell fate transitions. Current computational approaches to analyze chromatin modifications across multiple cell types do not model how the cell types are related on a lineage or over time. To overcome this limitation, we have developed a method called CMINT (Chromatin Module INference on Trees), a probabilistic clustering approach to systematically capture chromatin state dynamics across multiple cell types. Compared to existing approaches, CMINT can handle complex lineage topologies, capture higher quality clusters, and reliably detect chromatin transitions between cell types...
April 19, 2017: Genome Research
https://www.readbyqxmd.com/read/28413449/links-between-dna-methylation-and-nucleosome-occupancy-in-the-human-genome
#18
Clayton K Collings, John N Anderson
BACKGROUND: DNA methylation is an epigenetic modification that is enriched in heterochromatin but depleted at active promoters and enhancers. However, the debate on whether or not DNA methylation is a reliable indicator of high nucleosome occupancy has not been settled. For example, the methylation levels of DNA flanking CTCF sites are higher in linker DNA than in nucleosomal DNA, while other studies have shown that the nucleosome core is the preferred site of methylation. In this study, we make progress toward understanding these conflicting phenomena by implementing a bioinformatics approach that combines MNase-seq and NOMe-seq data and by comprehensively profiling DNA methylation and nucleosome occupancy throughout the human genome...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28408976/when-tads-go-bad-chromatin-structure-and-nuclear-organisation-in-human-disease
#19
REVIEW
Vera B Kaiser, Colin A Semple
Chromatin in the interphase nucleus is organised as a hierarchical series of structural domains, including self-interacting domains called topologically associating domains (TADs). This arrangement is thought to bring enhancers into closer physical proximity with their target genes, which often are located hundreds of kilobases away in linear genomic distance. TADs are demarcated by boundary regions bound by architectural proteins, such as CTCF and cohesin, although much remains to be discovered about the structure and function of these domains...
2017: F1000Research
https://www.readbyqxmd.com/read/28406749/nucleosome-repositioning-during-differentiation-of-a-human-myeloid-leukemia-cell-line
#20
Vladimir B Teif, Jan-Philipp Mallm, Tanvi Sharma, David B Mark Welch, Karsten Rippe, Roland Eils, Jörg Langowski, Ada L Olins, Donald E Olins
Cell differentiation is associated with changes in chromatin organization and gene expression. In this study, we examine chromatin structure following differentiation of the human myeloid leukemia cell line (HL-60/S4) into granulocytes with retinoic acid (RA) or into macrophage with phorbol ester (TPA). We performed ChIP-seq of histone H3 and its modifications, analyzing changes in nucleosome occupancy, nucleosome repeat length, eu-/heterochromatin redistribution and properties of epichromatin (surface chromatin adjacent to the nuclear envelope)...
March 4, 2017: Nucleus
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